Stapled peptides and uses thereof

Description

FIELD OF THE INVENTION

The present invention generally relates to cyclized peptides derived from the hyaluronan (HA)- and protein-binding region of RHAMM. The invention further relates to pharmaceutical compositions containing the peptides, and methods of using the peptides to detect the presence of HA in cells, for diagnosis of disorders or conditions associated with elevated levels of HA, for treatment of disorders or conditions associated with elevated levels of HA, for inhibiting proliferation or motility of cells, for inhibiting migration of cells, for preventing metastasis, for inhibiting inflammation, for inhibiting cellular invasion and for inhibiting fibrosis.

BACKGROUND OF THE INVENTION

Native hyaluronan (HA) is ubiquitous in its tissue distribution and in its high molecular form has anti-inflammatory properties [1-3]. HA fragments, which are produced as a result of tissue stress and oxygen/nitrogen free radical formation, function as pro-inflammatory Danger Associated Molecular Pattern molecules (DAMP) that interact with HA receptors and Toll-like receptors to promote monocyte maturation into macrophages, macrophage chemotaxis, and production of pro-inflammatory chemokines and iNOS [1, 2, 4]. Both CD44 and RHAMM (Receptor for Hyaluronan-Mediated Motility) have been functionally linked to Toll Like receptors 2 or 4 in the regulation of these macrophage functions [5-8]. Although CD44 clearly plays a key role in pro-inflammatory responses, CD44 is ubiquitous in its expression increasing the possibility of off target adverse effects [9] and its complex mechanisms for binding to HA present challenges [10, 11] to the design of antagonists. Collectively, these have limited the use of CD44 as a clinical target. In contrast to CD44, RHAMM is not constitutively expressed in most homeostatic tissues. Instead, RHAMM expression and in particular its cell surface display occurs transiently following tissue injury but is chronic in diseases involving sustained inflammation [3]. Not unexpectedly, the safety profile for RHAMM peptides is therefore good [12, 13]. Furthermore, HA binding to RHAMM, which occurs over a short sequence and depends on ionic interactions [14], is readily competed with peptide mimics.

Shorter versions of RHAMM have been proposed as pharmaceutically relevant peptides. However, it is well known that short linear peptides containing only natural L amino acids have very limited stability against protease hydrolysis in vivo.

SUMMARY OF THE INVENTION

A peptide is provided. The peptide comprises at least a portion of a RHAMM HA binding domain (HABD). The peptide has a length of at least 7 amino acids. The peptide includes one or more amino acid substitutions relative to the sequence of a HABD of a naturally occurring RHAMM protein. The one or more substitutions occur at position i, i+4, and/or i+7. The substitution allows for the formation of a covalent bond between the amino acid at position i and the amino acid at position i+4 or i+7.

Another peptide is provided. The peptide has a length of 20 amino acids or fewer. The peptide comprises an amino acid sequence having at least 75% identity to the amino acid sequence NLKQKIKHVVKLKDE (SEQ ID NO: 4).

Yet another peptide is provided. The peptide has a length of 20 amino acids or fewer. The peptide comprises an amino acid sequence having at least 70% sequence identity to the amino acid sequence VSKLRSQLVKRKQN (SEQ ID NO: 2). The peptide is acetylated at its amino-terminus.

Any of the peptides can further comprise a detectable label.

A pharmaceutical composition is provided. The pharmaceutical composition comprises one or more of any of the peptides and a pharmaceutically acceptable carrier.

A method for detecting the presence of hyaluronic acid in cells, tissues, or organs is provided. The method comprises contacting any of the peptides comprising a detectable label with the cell, tissue, or organ. An imaging technique is applied for detecting the detectable label.

A method for diagnosing a subject of a disorder or condition associated with elevated levels of hyaluronic acid (HA) or RHAMM is provided. The method comprises obtaining a cell or tissue sample from the subject. The sample is contacted with any of the peptides that comprises a detectable label. An imaging technique is applied for detecting the label in the sample. Detection of elevated HA levels in the sample indicates a positive diagnosis of the disorder or condition.

A method for treating a subject suffering from a disorder or condition associated with elevated levels of hyaluronic acid (HA) or RHAMM is provided. The method comprises administering to the subject an effective amount of one or more peptides of any of the peptides or any of the pharmaceutical compositions.

A method of inhibiting proliferation or motility of cells that express elevated levels of RHAMM or that have elevated levels of HA is provided. The method comprises contacting the cells with an effective amount of one or more of any of the peptides or any of the pharmaceutical compositions.

A method of preventing metastasis in a subject having cancer is provided. The method comprises administering to the subject an effective amount of one or more of any of the peptides or any of the pharmaceutical compositions.

A method for inhibiting migration of cells is provided. The method comprises contacting the cells with an effective amount of one or more of any of the peptides or any of the pharmaceutical compositions.

A method for inhibiting inflammation is provided. The method comprises contacting cells with an effective amount of one or more of any of the peptides or any of the pharmaceutical compositions.

A method for inhibiting cellular invasion is provided. The method comprises contacting cells with an effective amount of one or more of any of the peptides or any of the pharmaceutical compositions.

A method for inhibiting fibrosis is provided. The method comprises contacting cells with an effective amount of one or more or any of the peptides or any of the pharmaceutical compositions.

Other objects and features will be in part apparent and in part pointed out hereinafter.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows the sequence for amino acids 706-767 of RHAMM. This sequence is also referred to herein as “7 kDa RHAMM.” Two minimal HA binding domains are shown the boxes labeled “BD1” and “BD2.” The lowercase letters under the sequence indicate helical regions (“h”), coiled regions (“c”), and extended strands (“e”).

FIG. 2 provides illustrative ELISA results.

FIG. 3 depicts: (a) a lactam bridge; (b) a hydrocarbon bridge; (c) a metal-ion clip; (d) a hydrogen bond surrogate; and (e) formation of a heterocycle bridge by azide-alkyne cycloaddition.

FIG. 4 provides the structure for the Grubbs ruthenium catalyst.

FIG. 5 provides an illustrative reaction scheme for standard Fmoc solid-phase peptide synthesis (SPPS).

FIG. 6 provides an illustrative reaction scheme for synthesis of a peptide having allyl glycine substitutions that allow for cyclization of the peptide.

FIG. 7 provides an illustrative reaction scheme for synthesis of a peptide containing glutamic acid residues protected with allylester (Glu(OAll)) and lysine residues protected with alloxycarbonyl (Lys(Alloc)) protecting groups.

FIG. 8 provides an illustrative reaction scheme for deprotection of Glu(OAll) and Lys(Alloc) residues in a peptide and formation of a lactam bridge.

FIG. 9 provides an illustrative reaction scheme for deprotection of remaining protecting groups in a synthesized peptide and cleavage of peptides off of resin to obtain lactam bridged cyclic peptides.

FIG. 10 provides illustrative circular dichroism (CD) spectra for 7 kDa RHAMM (SEQ ID NO: 1) and the linear peptide VSKLRSQLVKRKQN (SEQ ID NO: 2) and cyclized variants thereof.

FIG. 11 illustrates the RHAMM HA binding region.

FIGS. 12-15 provide illustrative CD data for linear and cyclized peptides.

FIGS. 16-38 provide illustrative CD spectra for linear and cyclized peptides.

FIGS. 39 and 40 provide illustrative data from a direct HA-binding assay.

FIGS. 41-43 provide illustrative data from a cell migration assay.

FIGS. 44-46 provide illustrative data from an assay that measures inflammation.

FIGS. 47 and 48 provide illustrative data from an assay that measures fibrosis.

FIGS. 49 and 50 provide illustrative data from a cell invasion assay.

Corresponding reference characters indicate corresponding parts throughout the drawings.

Definitions

When the articles “a,” “an,” “one,” “the,” and “said” are used herein, they mean “at least one” or “one or more” unless otherwise indicated.

The term “amino acid” as used herein is meant to include both naturally occurring and synthetic (non-naturally occurring) amino acids.

The term “standard amino acid” as used herein refers to any of the twenty standard L-amino acids that are commonly found in naturally occurring peptides in humans and animals, namely the L-isomers of alanine (Ala or A), Arginine (Arg or R), asparagine (Asn or N), aspartic acid (Asp or D), cysteine (Cys or C), glutamic acid (Glu or E), glutamine (Glu or Q), glycine (Gly or G), histidine (His or H), isoleucine (Ile or I), leucine (Leu or L), lysine (Lys or K), methionine (Met or M), phenylalanine (Phe or F), proline (Pro or P), serine (Ser or S), threonine (Thr or T), tryptophan (Trp or W), tyrosine (Tyr or Y), and valine (Val or V).

The term “non-standard amino acid” as used herein refers to any amino acid other than the standard amino acids, regardless of whether it is prepared synthetically or isolated or otherwise derived from a natural source. Thus, the term “non-standard amino acid” encompasses both naturally occurring amino acids that are not standard amino acids, as well as non-naturally occurring amino acids.

The term “naturally occurring amino acid” as used herein includes all twenty of the standard L-amino acids that are commonly found in naturally occurring peptides, as well as any other amino acid found in nature. Examples of non-standard naturally occurring amino acids include, but are not limited to ornithine and L-2-aminoadipic acid. Naturally occurring non-standard amino acids typically do not participate in protein translation at the ribosome of a cell in nature. However, they occur in nature and may participate in other physiological processes.

The term “non-naturally occurring amino acid” as used herein refers to any amino acid that does not occur in nature but instead is generated through chemical synthesis or through chemical modification of a naturally occurring amino acid.

The terms “comprising,” “including,” and “having” are intended to be inclusive and mean that there may be additional elements other than the listed elements.

The term “effective amount” as used herein refers to an amount sufficient to induce a detectable therapeutic response in a subject.

Unless otherwise specified, the terms “HABD1” and “HABD2” as used herein refer to the minimal hyaluronan-binding domains of RHAMM as depicted in FIGS. 1 and 11.

The term “peptide” as used herein refers a short chain of amino acids linked to one another via peptide bonds. Peptides generally have a length of fewer than about 50 amino acids.

The term “isolated peptide” as used herein refers to a peptide which is substantially separated from other cellular components.

The terms “stapled peptide” and “cyclized peptide” are used interchangeably herein to refer to a peptide that includes a covalent bond between the side chains of two amino acids in the peptide, or between the amino-terminal nitrogen of a peptide and an amino acid side chain of another amino acid within the peptide. The term “peptide staple” refers to the covalent bond between the two amino acid side chains.

The terms “i,” “i+4,” and “i+7” as used herein refer to the positions of the amino acids within the peptide that become covalently bonded to one another upon formation of the staple. The “i” position refers to the position of the amino acid that is nearest to the amino terminus of the peptide. The “i+4” position is 4 amino acids downstream (4 amino acids further towards the carboxy-terminus) of the “i” position, and the “i+7” position is 7 amino acids downstream of the “i” position. Upon formation of the staple, a covalent bond is formed between the amino acid at position i and the amino acid at position i+4 or i+7.

The term “RHAMM” as used herein refers to a Receptor for Hyaluronic Acid Mediated Motility, also known as CD 168. RHAMM is a non-integral cell surface (CD 168) and intracellular hyaluronan binding protein that promotes cell motility in vitro and whose expression is strongly upregulated in aggressive tumors [WO 2008/140587].

The term “subject” as used herein refers to any mammal, including both humans and non-human mammals.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

The present invention relates to peptides derived from the hyaluronan (HA)- and protein-binding region of RHAMM and cyclized derivatives of such peptides. FIGS. 1 and 11 depict the HA-binding region of RHAMM. FIG. 1 shows amino acids 706-767 of the mouse RHAMM sequence. In FIG. 1, the minimal HA binding domains are indicated shown the boxes labeled “BD1” and “BD2.” The lowercase letters under the sequence indicate helical regions (“h”), coiled regions (“c”), and extended strands (“e”).

FIG. 11 provides a more detailed depiction of the HA- and protein-binding region of RHAMM. RHAMM regulates cell motility and stem cell differentiation. These functions have been linked to the HA binding capability of RHAMM and also its intracellular association with proteins such as ERK, TPX2, AURKA and tubulin. As shown in FIG. 11, The HA binding sequence of RHAMM contains two domains (underlined sequences, HA-binding domain 1 (HABD1) and HA-binding domain 2 (HABD2) that contribute to binding to HA. These are separated by a leucine zipper (leucines that form zipper are in grey and whole region is denoted by a solid double arrow) that is required for binding of RHAMM to tubulin, TPX2 and AURKA. The second HA domain (HABD2) contains the most sequences that are thought to be required for HA binding and is more important for binding to HA than HABD1. The amino acids that have been shown to be involved in HA binding (either by site directed mutagenesis or computer modelling) are enlarged. HABD1 also contains sequence that is involved in docking of the MAP kinase ERK1 to RHAMM, as shown by site directed mutagenesis. This region is identified by a dotted double arrow. Minimal HA binding sequences are marked by double underlines.

Stapled Peptides

Stapled peptides include a covalent bond between the side chains of two amino acids in the peptide. Peptide stapling can be used to physically constrain a peptide into a specific conformation (e.g., to physically constrain a peptide into its native alpha-helical state). This can in turn enhance the pharmacological properties of a peptide by helping to retain the native structure needed to interact with a target molecule, increasing cell penetration, and/or protecting the peptide from proteolytic degradation.

Peptide stapling was used to constrain alpha-helical structures in peptides derived from the HA-binding region of RHAMM. These peptides contained HABD1 (“HABD1” peptides), HABD2 (“HABD2” peptides), or most or all of HABD1 and all of HABD2 (“HABD1+HABD2” peptides). Since the alpha helical structures of the HABD1 and HABD2 of RHAMM are predicted to be required for HA binding and since the HA binding properties of RHAMM are known to be key to its biological activity, a variety of stapled peptides were developed that can be grouped into HABD1, HABD2, and sequences containing both HABD1 and HABD2 (HABD1+HABD2). The leucine zipper and HABD1 are also regions of protein:protein interactions that require alpha helicity. Therefore, stapling these peptides could also increase the ability of the peptides to affect these interactions. The peptides thus have potentially multiple protein partners with which they may compete. It was unknown prior to the present invention whether short alpha-helical segments of RHAMM would allow for retention of HA binding and/or biological activity.

When peptide staples are used to physically constrain a peptide into its native alpha-helical state, it is desirable to form the staple between the i and i+4 positions of a peptide or between the i and i+7 positions of a peptide. This because upon formation of the alpha helix, the amino acid side chains of the amino acids at the i, i+4, and i+7 positions will be located on the same face of the helix.

A number of different types of peptide staples can be used. FIG. 3 illustrates several types of peptide staples: (a) a lactam bridge; (b) a hydrocarbon bridge; (c) a metal-ion clip; (d) a hydrogen bond surrogate; and (e) a heterocycle bridge. Any of these types of staples, or other peptide staples known in the art, can be used in connection with any of the peptides described herein.

Lactam bridges can be formed glutamic acid and lysine residues of a peptides. The glutamic acid and lysine residues may be present in the native sequence of the peptide. Alternatively, amino acid substitutions for glutamic acid and/or lysine at the desired positions of the peptide or may be introduced at the desired positions during peptide synthesis. When glutamic acid and lysine are used to form lactam bridges, protected versions of these amino acids are introduced into the peptide during synthesis. In particular, ester-protected glutamic acid (Glu(OAll)) residues and allyloxycarbonyl-protected lysine residues can be used. Following peptide synthesis, the protecting groups are removed and the lactam bridge is formed between the glutamic acid and lysine residues. This process is illustrated in FIGS. 7-9.

Thus, for example, a glutamic acid can be introduced at position i, and a lysine introduced at position i+4, allow for formation of a lactam bridge between the i and i+4 residues. Alternatively, a glutamic acid can be introduced at position i, and a lysine introduced at position i+7, such that a lactam bridge can be formed between the i and i+7 residues.

Using a glutamic acid residue at the i position and a lysine residue at the i+4 or i+7 position is the typical way to form this type of lactam bridge. However, the order of the lysine and glutamic acid residues can also be reversed. For example, a lysine residue can be introduced at position i of a peptide and a glutamic acid residue can be introduced at the i+4 or i+7 position of the peptide. This type of staple is referred to herein as a “reverse” lactam bridge, since the typical order of the glutamic acid and lysine residues is reversed.

Lactam bridges can also be formed between ornithine (Orn) and L-2-aminoadipic acid (Aad) residues. The ornithine and L-2-aminoadipic acid residues can be introduced at the desired positions during peptide synthesis, and then the lactam bridge can be formed using standard methods known in the art.

Hydrocarbon bridges (e.g., olefin bridges) can be formed between two allylglycine residues in a peptide. Allylglycine (AllylGly) has the following structure:

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Two allylglycine residues can be introduced into a peptide at the desired positions, and then the hydrocarbon bridge can be formed using standard methods known in the art. When allylglycine residues are used for formation of hydrocarbon bridges, the substitutions are preferably made at the i and i+4 positions of the peptide.

Hydrocarbon bridges can also be formed using the alanine derivatives S5, R8, and/or R5. The alanine derivatives R5 and R8 both have the following structure:

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In R8 m is 5. In R5, m is 2. The alanine derivatives S5 has the structure shown below, wherein n is 2:

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The following preferred configurations can be used to create hydrocarbon bridges in peptides using the alanine derivatives S5, R8, and/or R5: (1) substitution at position i of a peptide with an S5 residue and substitution at position i+4 with another S5 residue; (2) substitution at position i of a peptide with an R5 residue and substitution at position i+4 with another R5 residue; or (3) substitution at position i of a peptide with an R8 residue and substitution at position i+7 with an S5 residue. It has also been reported that substitution at the i position with an R5 residue and substitution at the i+3 position with an S5 residue can also be used for helix stabilization.

Following introduction of the alanine derivatives or allylglycine residues at the desired positions of the peptide, a hydrocarbon bridge can be formed between the olefin tether side chains of these amino acids. The olefin tethers can react with a Grubbs ruthenium catalyst (see FIG. 4) to complete the ring closing reaction.

In a metal-ion clip, a bridge is formed through coordinate bonds to a metal-ion (e.g., a rhenium, ruthenium, or palladium ion).

In a hydrogen bond surrogate, a hydrocarbon bridge is formed between the amino-terminal nitrogen atom of a peptide to an amino acid side chain.

Another type of peptide staple is a heterocycle bridge. Heterocycle bridges are formed through a cycloaddition reaction between two amino acids, for example azide-alkyne cycloaddition as shown in panel (e) of FIG. 3.

Peptides can be synthesized that contain two or more of any of the peptide staples discussed above. For example, to prepare a peptide having multiple lactam bridge staples, the peptide is synthesized until the amino acid residue at the end of the first staple. With the N-terminal Fmoc protecting group still present, the Alloc and Allyl protecting groups are deprotected and cyclized to form the first staple. Peptide synthesis is then continued and deprotection and cyclization are repeated to form the second staple.

The present invention is directed to a peptide comprising at least a portion of a RHAMM HA binding domain (HABD). The peptide has a length of at least 7 amino acids. The peptide includes one or more amino acid substitutions relative to the sequence of a HABD of a naturally occurring RHAMM protein. The one or more substitutions occur at position i, i+4, and/or i+7. The substitution allows for the formation of a covalent bond between the amino acid at position i and the amino acid at position i+4 or i+7.

The substitution at position i, i+4, and/or i+7 can comprise a substitution with a standard amino acid.

The substitution at position i, i+4, and/or i+7 can comprise a substitution with a non-standard amino acid.

The non-standard amino acid can comprise a naturally occurring amino acid.

The non-standard amino acid can comprise a non-naturally occurring amino acid.

The amino acid at position i is preferably covalently bonded to the amino acid at position i+4 or i+7.

For example, the amino acid at position i can be covalently bonded to the amino acid at position i+4.

Alternatively, the amino acid at position i can be covalently bonded to the amino acid at position i+7.

The covalent bond can comprise a lactam bridge, a hydrocarbon bridge, a metal-ion clip, a hydrogen bond surrogate, or a heterocycle bridge.

The covalent bond suitably comprises a lactam bridge or a hydrocarbon bridge.

For example, the covalent bond can comprise a lactam bridge.

Where the covalent bond comprises a lactam bridge, the one or more amino acid substitutions can comprise a substitution with a glutamic acid residue, a lysine residue, or a combination thereof.

For example, where the covalent bond comprises a lactam bridge, the one or more amino acid substitutions can comprise a substitution with a glutamic acid residue at position i.

Where the covalent bond comprises a lactam bridge, the one or more amino acid substitutions can comprise a substitution with a glutamic acid residue at position i+4.

Where the covalent bond comprises a lactam bridge, the one or more amino acid substitutions can comprise a substitution with a glutamic acid residue at position i+7.

Where the covalent bond comprises a lactam bridge, the one or more amino acid substitutions can comprise a substitution with a lysine residue at position i.

Where the covalent bond comprises a lactam bridge, the one or more amino acid substitutions can comprise a substitution with a lysine residue at position i+4.

Where the covalent bond comprises a lactam bridge, the one or more amino acid substitutions can comprise a substitution with a lysine residue at position i+7.

Where the covalent bond comprises a lactam bridge and the one or more amino acid substitutions comprises the substitution with the glutamic acid residue at position i, the sequence of the HABD of the naturally occurring RHAMM protein can comprise a lysine residue at position i+4 or position i+7. For example, the sequence of the HABD of the naturally occurring RHAMM protein can comprises the lysine residue at position i+4.

Where the covalent bond comprises a lactam bridge and the one or more amino acid substitutions comprises the substitution with the lysine residue at position i+4 or i+7, the sequence of the HABD of the naturally occurring RHAMM protein can comprise a glutamic acid residue at position i.

Where the covalent bond comprises a lactam bridge and the one or more amino acid substitutions comprises the substitution with the lysine residue at position i, the sequence of the HABD of the naturally occurring RHAMM protein can comprise a glutamic acid residue at position i+4 or i+7.

Where the covalent bond comprises a lactam bridge and the one or more amino acid substitutions comprises the substitution with the glutamic acid residue at position i+4 or i+7, the sequence of the HABD of the naturally occurring RHAMM protein can comprise a lysine residue at position i.

Where the covalent bond comprises a lactam bridge and the one or more amino acid substitutions comprises the substitution with a glutamic acid residue at position i, the one or more amino acid substitutions can further comprise the substitution with the lysine residue at position i+4 or the substitution with the lysine residue at position i+7. For example, the substitution with the lysine residue can be at position i+4.

Where the covalent bond comprises a lactam bridge and the one or more amino acid substitutions comprises the substitution with a lysine residue at position i, the one or more substitutions can further comprise the substitution with the glutamic acid residue at position i+4 or the substitution with the glutamic acid residue at position i+7.

Where the covalent bond comprises a lactam bridge, the one or more amino acid substitutions can comprise a substitution with an ornithine residue at position i and a substitution with an L-2-aminoadipic acid residue at position i+4 or i+7.

Alternatively, where the covalent bond comprises a lactam bridge, the one or more amino acid substitutions can comprise a substitution with an L-2-aminoadipic acid residue at position i and a substitution with an ornithine residue at position i+4 or i+7.

The covalent bond can comprise a hydrocarbon bridge. Where the covalent bond comprises the hydrocarbon bridge, the one or more amino acid substitutions can comprise substitutions with allylglycine residues at positions i and i+4.

Where the covalent bond comprises the hydrocarbon bridge, the one or more substitutions can comprise substitutions with alanine derivative S5 residues at positions i and i+4.

Where the covalent bond comprises the hydrocarbon bridge, the one or more substitutions can comprise a substitution with alanine derivative R8 at position i and a substitution with alanine derivative S5 at one of positions i+4 and i+7.

Where the covalent bond comprises the hydrocarbon bridge, the one or more substitutions can comprise substitutions with alanine derivative R5 residues at positions i and i+4.

Any of the peptides can comprise two or more staples. For example, the peptide can comprise one or more first substitutions at a first position i, a first position i+4, and/or a first position i+7, wherein the one or more first substitutions allows for the formation of a covalent bond between the amino acid at first position i and the amino acid at first position i+4 or first position i+7; and one or more second substitutions at a second position i, a second position i+4, and/or a second position i+7, wherein the one or more second substitutions allows for the formation of a covalent bond between the amino acid at second position i and the amino acid at second position i+4 or second position i+7.

Any of the peptides can have a length of at least 8 amino acids.

Any of the peptides can have a length of at least 9 amino acids.

Any of the peptides can have a length of at least 10 amino acids.

Any of the peptides can have a length of at least 11 amino acids.

Any of the peptides can have a length of at least 12 amino acids.

Any of the peptides can have a length of at least 13 amino acids.

Any of the peptides can have a length of at least 14 amino acids.

Any of the peptides preferably has a length of 50 amino acids or fewer.

For example, any of the peptides can have a length of 45 amino acids or fewer.

Any of the peptides can have a length of 40 amino acids or fewer.

Any of the peptides can have a length of 36 amino acids or fewer.

Any of the peptides can have a length of 30 amino acids or fewer.

Any of the peptides can have a length of 20 amino acids or fewer.

Any of the peptides can have a length of 19 amino acids or fewer.

Any of the peptides can have a length of 18 amino acids or fewer.

Any of the peptides can have a length of 17 amino acids or fewer.

Any of the peptides can have a length of 16 amino acids or fewer.

Any of the peptides can have a length of 15 amino acids or fewer.

Any of the peptides can have a length of 14 amino acids or fewer.

For example, any of the peptides can have a length of 8-16 amino acids.

In any of the peptides, the RHAMM HABD can comprises amino acids 14 to 24 of SEQ ID NO: 1.

In any of the peptides, the RHAMM HABD can comprise amino acids 36 to 45 of SEQ ID NO: 1.

In any of the peptides, the RHAMM HABD can comprise amino acids 14 to 24 and amino acids 36 to 45 of SEQ ID NO: 1.

In any of the peptides, the amino acid sequence of the peptide can comprise a sequence selected from SEQ ID NOs. 2-6, wherein the sequence includes the one or more amino acid substitutions.

In any of the peptides, the amino acid sequence of the peptide can consist of a sequence selected from SEQ ID NOs. 2-6, wherein the sequence includes the one or more amino acid substitutions.

Any of the peptides can comprise an amino acid sequence selected from SEQ ID NOs. 7-32.

Any of the peptides can consist of an amino acid sequence selected from SEQ ID NOs. 7-32.

The amino acid sequence of the peptide can comprise VSKX₁RSQX₂VKRKQN (SEQ ID NO: 7), wherein X₁is glutamic acid and X₂is lysine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of VSKX₁RSQX₂VKRKQN (SEQ ID NO: 7), wherein X₁is glutamic acid and X₂is lysine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise VSKLX₁SQLX₂KRKQN (SEQ ID NO: 8), wherein X₁is glutamic acid and X₂is lysine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of VSKLX₁SQLX₂KRKQN (SEQ ID NO: 8), wherein X₁is glutamic acid and X₂is lysine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise VSKLRX₁QLVX₂RKQN (SEQ ID NO: 9), wherein X₁is glutamic acid and X₂is lysine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of VSKLRX₁QLVX₂RKQN (SEQ ID NO: 9), wherein X₁is glutamic acid and X₂is lysine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise VSKLRSX₁LVKX₂KQN (SEQ ID NO: 10), wherein X₁is glutamic acid and X₂is lysine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of VSKLRSX₁LVKX₂KQN (SEQ ID NO: 10), wherein X₁is glutamic acid and X₂is lysine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise VSKX₁RSQX₂VKRKQN (SEQ ID NO: 7), wherein X₁is lysine and X₂is glutamic acid, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of VSKX₁RSQX₂VKRKQN (SEQ ID NO: 7), wherein X₁is lysine and X₂is glutamic acid, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise VSKLX₁SQLX₂KRKQN (SEQ ID NO: 8), wherein X₁is lysine and X₂is glutamic acid, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of VSKLX₁SQLX₂KRKQN (SEQ ID NO: 8), wherein X₁is lysine and X₂is glutamic acid, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise VSKLRX₁QLVX₂RKQN (SEQ ID NO: 9), wherein X₁is lysine and X₂is glutamic acid, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of VSKLRX₁QLVX₂RKQN (SEQ ID NO: 9), wherein X₁is lysine and X₂is glutamic acid, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise VSKLRSX₁LVKX₂KQN (SEQ ID NO: 10), wherein X₁is lysine and X₂is glutamic acid, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of VSKLRSX₁LVKX₂KQN (SEQ ID NO: 10), wherein X₁is lysine and X₂is glutamic acid, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise VSKX₁RSQX₂VKRKQN (SEQ ID NO: 7), wherein X₁is ornithine and X₂is L-2-aminoadipic acid, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of VSKX₁RSQX₂VKRKQN (SEQ ID NO: 7), wherein X₁is ornithine and X₂is L-2-aminoadipic acid, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise VSKLX₁SQLX₂KRKQN (SEQ ID NO: 8), wherein X₁is ornithine and X₂is L-2-aminoadipic acid, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of VSKLX₁SQLX₂KRKQN (SEQ ID NO: 8), wherein X₁is ornithine and X₂is L-2-aminoadipic acid, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise VSKLRX₁QLVX₂RKQN (SEQ ID NO: 9), wherein X₁is ornithine and X₂is L-2-aminoadipic acid, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of VSKLRX₁QLVX₂RKQN (SEQ ID NO: 9), wherein X₁is ornithine and X₂is L-2-aminoadipic acid, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise VSKLRSX₁LVKX₂KQN (SEQ ID NO: 10), wherein X₁is ornithine and X₂is L-2-aminoadipic acid, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of VSKLRSX₁LVKX₂KQN (SEQ ID NO: 10), wherein X₁is ornithine and X₂is L-2-aminoadipic acid, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise VSKX₁RSQX₂VKRKQN (SEQ ID NO: 7), wherein X₁is L-2-aminoadipic acid and X₂is ornithine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of VSKX₁RSQX₂VKRKQN (SEQ ID NO: 7), wherein X₁is L-2-aminoadipic acid and X₂is ornithine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise VSKLX₁SQLX₂KRKQN (SEQ ID NO: 8), wherein X₁is L-2-aminoadipic acid and X₂is ornithine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of VSKLX₁SQLX₂KRKQN (SEQ ID NO: 8), wherein X₁is L-2-aminoadipic acid and X₂is ornithine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise VSKLRX₁QLVX₂RKQN (SEQ ID NO: 9), wherein X₁is L-2-aminoadipic acid and X₂is ornithine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of VSKLRX₁QLVX₂RKQN (SEQ ID NO: 9), wherein X₁is L-2-aminoadipic acid and X₂is ornithine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise VSKLRSX₁LVKX₂KQN (SEQ ID NO: 10), wherein X₁is L-2-aminoadipic acid and X₂is ornithine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of VSKLRSX₁LVKX₂KQN (SEQ ID NO: 10), wherein X₁is L-2-aminoadipic acid and X₂is ornithine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise VSKX₁RSQX₂VKRKQN (SEQ ID NO: 7), wherein X₁and X₂are both alanine derivative S5, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of VSKX₁RSQX₂VKRKQN (SEQ ID NO: 7), wherein X₁and X₂are both alanine derivative S5, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise VSKLX₁SQLX₂KRKQN (SEQ ID NO: 8), wherein X₁and X₂are both alanine derivative S5, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of VSKLX₁SQLX₂KRKQN (SEQ ID NO: 8), wherein X₁and X₂are both alanine derivative S5, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise VSKLRX₁QLVX₂RKQN (SEQ ID NO: 9), wherein X₁and X₂are both alanine derivative S5, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of VSKLRX₁QLVX₂RKQN (SEQ ID NO: 9), wherein X₁and X₂are both alanine derivative S5, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise VSKLRSX₁LVKX₂KQN (SEQ ID NO: 10), wherein X₁and X₂are both alanine derivative S5, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of VSKLRSX₁LVKX₂KQN (SEQ ID NO: 10), wherein X₁and X₂are both alanine derivative S5, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise VSKX₁RSQX₂VKRKQN (SEQ ID NO: 7), wherein X₁and X₂are both allylglycine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of VSKX₁RSQX₂VKRKQN (SEQ ID NO: 7), wherein X₁and X₂are both allylglycine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise VSKLX₁SQLX₂KRKQN (SEQ ID NO: 8), wherein X₁and X₂are both allylglycine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of VSKLX₁SQLX₂KRKQN (SEQ ID NO: 8), wherein X₁and X₂are both allylglycine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise VSKLRX₁QLVX₂RKQN (SEQ ID NO: 9), wherein X₁and X₂are both allylglycine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of VSKLRX₁QLVX₂RKQN (SEQ ID NO: 9), wherein X₁and X₂are both allylglycine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise VSKLRSX₁LVKX₂KQN (SEQ ID NO: 10), wherein X₁and X₂are both allylglycine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of VSKLRSX₁LVKX₂KQN (SEQ ID NO: 10), wherein X₁and X₂are both allylglycine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise NLKX₁KIKX₂VVKLKDE (SEQ ID NO: 15), wherein X₁is glutamic acid and X₂is lysine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of NLKX₁KIKX₂VVKLKDE (SEQ ID NO: 15), wherein X₁is glutamic acid and X₂is lysine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise NLKQX₁KHX₂VKLKDE (SEQ ID NO: 16), wherein X₁is glutamic acid and X₂is lysine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of NLKQX₁KHX₂VKLKDE (SEQ ID NO: 16), wherein X₁is glutamic acid and X₂is lysine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise NLKQKX₁KHVX₂KLKDE (SEQ ID NO: 17), wherein X₁is glutamic acid and X₂is lysine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of NLKQKX₁KHVX₂KLKDE (SEQ ID NO: 17), wherein X₁is glutamic acid and X₂is lysine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise NLKQKIX₁HVVX₂LKDE (SEQ ID NO: 18), wherein X₁is glutamic acid and X₂is lysine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of NLKQKIX₁HVVX₂LKDE (SEQ ID NO: 18), wherein X₁is glutamic acid and X₂is lysine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise NLKQKIKX₁VVKX₂KDE (SEQ ID NO: 19), wherein X₁is glutamic acid and X₂is lysine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of NLKQKIKX₁VVKX₂KDE (SEQ ID NO: 19), wherein X₁is glutamic acid and X₂is lysine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise NLKX₁KIKX₂VVKLKDE (SEQ ID NO: 15), wherein X₁is lysine and X₂is glutamic acid, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of NLKX₁KIKX₂VVKLKDE (SEQ ID NO: 15), wherein X₁is lysine and X₂is glutamic acid, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise NLKQX₁IKHX₂VKLKDE (SEQ ID NO: 16), wherein X₁is lysine and X₂is glutamic acid, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of NLKQX₁IKHX₂VKLKDE (SEQ ID NO: 16), wherein X₁is lysine and X₂is glutamic acid, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise NLKQKX₁KHVX₂KLKDE (SEQ ID NO: 17), wherein X₁is lysine and X₂is glutamic acid, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of NLKQKX₁KHVX₂KLKDE (SEQ ID NO: 17), wherein X₁is lysine and X₂is glutamic acid, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise NLKQKIX₁HVVX₂LKDE (SEQ ID NO: 18), wherein X₁is lysine and X₂is glutamic acid, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of NLKQKIX₁HVVX₂LKDE (SEQ ID NO: 18), wherein X₁is lysine and X₂is glutamic acid, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise NLKQKIKX₁VVKX₂KDE (SEQ ID NO: 19), wherein X₁is lysine and X₂is glutamic acid, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of NLKQKIKX₁VVKX₂KDE (SEQ ID NO: 19), wherein X₁is lysine and X₂is glutamic acid, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise NLKX₁KIKX₂VVKLKDE (SEQ ID NO: 15), wherein X₁is ornithine and X₂is L-2-aminoadipic acid, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of NLKX₁KIKX₂VVKLKDE (SEQ ID NO: 15), wherein X₁is ornithine and X₂is L-2-aminoadipic acid, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise NLKQX₁IKHX₂VKLKDE (SEQ ID NO: 16), wherein X₁is ornithine and X₂is L-2-aminoadipic acid, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of NLKQX₁IKHX₂VKLKDE (SEQ ID NO: 16), wherein X₁is ornithine and X₂is L-2-aminoadipic acid, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise NLKQKX₁KHVX₂KLKDE (SEQ ID NO: 17), wherein X₁is ornithine and X₂is L-2-aminoadipic acid, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of NLKQKX₁KHVX₂KLKDE (SEQ ID NO: 17), wherein X₁is ornithine and X₂is L-2-aminoadipic acid, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise NLKQKIX₁HVVX₂LKDE (SEQ ID NO: 18), wherein X₁is ornithine and X₂is L-2-aminoadipic acid, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of NLKQKIX₁HVVX₂LKDE (SEQ ID NO: 18), wherein X₁is ornithine and X₂is L-2-aminoadipic acid, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise NLKQKIKX₁VVKX₂KDE (SEQ ID NO: 19), wherein X₁is ornithine and X₂is L-2-aminoadipic acid, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of NLKQKIKX₁VVKX₂KDE (SEQ ID NO: 19), wherein X₁is ornithine and X₂is L-2-aminoadipic acid, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise NLKX₁KIKX₂VVKLKDE (SEQ ID NO: 15), wherein X₁is L-2-aminoadipic acid and X₂is ornithine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of NLKX₁KIKX₂VVKLKDE (SEQ ID NO: 15), wherein X₁is L-2-aminoadipic acid and X₂is ornithine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise NLKQX₁IKHX₂VKLKDE (SEQ ID NO: 16), wherein X₁is L-2-aminoadipic acid and X₂is ornithine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of NLKQX₁IKHX₂VKLKDE (SEQ ID NO: 16), wherein X₁is L-2-aminoadipic acid and X₂is ornithine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise NLKQKX₁KHVX₂KLKDE (SEQ ID NO: 17), wherein X₁is L-2-aminoadipic acid and X₂is ornithine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of NLKQKX₁KHVX₂KLKDE (SEQ ID NO: 17), wherein X₁is L-2-aminoadipic acid and X₂is ornithine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise NLKQKIX₁HVVX₂LKDE (SEQ ID NO: 18), wherein X₁is L-2-aminoadipic acid and X₂is ornithine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of NLKQKIX₁HVVX₂LKDE (SEQ ID NO: 18), wherein X₁is L-2-aminoadipic acid and X₂is ornithine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise NLKQKIKX₁VVKX₂KDE (SEQ ID NO: 19), wherein X₁is L-2-aminoadipic acid and X₂is ornithine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of NLKQKIKX₁VVKX₂KDE (SEQ ID NO: 19), wherein X₁is L-2-aminoadipic acid and X₂is ornithine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise NLKX₁KIKX₂VVKLKDE (SEQ ID NO: 15), wherein X₁and X₂are both alanine derivative S5, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of NLKX₁KIKX₂VVKLKDE (SEQ ID NO: 15), wherein X₁and X₂are both alanine derivative S5, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise NLKQX₁IKHX₂VKLKDE (SEQ ID NO: 16), wherein X₁and X₂are both alanine derivative S5, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of NLKQX₁IKHX₂VKLKDE (SEQ ID NO: 16), wherein X₁and X₂are both alanine derivative S5, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise NLKQKX₁KHVX₂KLKDE (SEQ ID NO: 17), wherein X₁and X₂are both alanine derivative S5, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of NLKQKX₁KHVX₂KLKDE (SEQ ID NO: 17), wherein X₁and X₂are both alanine derivative S5, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise NLKQKIX₁HVVX₂LKDE (SEQ ID NO: 18), wherein X₁and X₂are both alanine derivative S5, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of NLKQKIX₁HVVX₂LKDE (SEQ ID NO: 18), wherein X₁and X₂are both alanine derivative S5, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise NLKQKIKX₁VVKX₂KDE (SEQ ID NO: 19), wherein X₁and X₂are both alanine derivative S5, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of NLKQKIKX₁VVKX₂KDE (SEQ ID NO: 19), wherein X₁and X₂are both alanine derivative S5, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise NLKX₁KIKX₂VVKLKDE (SEQ ID NO: 15), wherein X₁and X₂are both allylglycine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of NLKX₁KIKX₂VVKLKDE (SEQ ID NO: 15), wherein X₁and X₂are both allylglycine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise NLKQX₁IKHX₂VKLKDE (SEQ ID NO: 16), wherein X₁and X₂are both allylglycine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of NLKQX₁IKHX₂VKLKDE (SEQ ID NO: 16), wherein X₁and X₂are both allylglycine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise NLKQKX₁KHVX₂KLKDE (SEQ ID NO: 17), wherein X₁and X₂are both allylglycine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of NLKQKX₁KHVX₂KLKDE (SEQ ID NO: 17), wherein X₁and X₂are both allylglycine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise NLKQKIX₁HVVX₂LKDE (SEQ ID NO: 18), wherein X₁and X₂are both allylglycine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of NLKQKIX₁HVVX₂LKDE (SEQ ID NO: 18), wherein X₁and X₂are both allylglycine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise NLKQKIKX₁VVKX₂KDE (SEQ ID NO: 19), wherein X₁and X₂are both allylglycine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of NLKQKIKX₁VVKX₂KDE (SEQ ID NO: 19), wherein X₁and X₂are both allylglycine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise NLKX₁KIKHVVX₂LKDE (SEQ ID NO: 20), wherein X₁is glutamic acid and X₂is lysine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of NLKX₁KIKHVVX₂LKDE (SEQ ID NO: 20), wherein X₁is glutamic acid and X₂is lysine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise NLKQX₁IKHVVKX₂KDE (SEQ ID NO: 21), wherein X₁is glutamic acid and X₂is lysine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of NLKQX₁IKHVVKX₂KDE (SEQ ID NO: 21), wherein X₁is glutamic acid and X₂is lysine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise NLKX₁KIKHVVX₂LKDE (SEQ ID NO: 20), wherein X₁is lysine and X₂is glutamic acid, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of NLKX₁KIKHVVX₂LKDE (SEQ ID NO: 20), wherein X₁is lysine and X₂is glutamic acid, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise NLKQX₁IKHVVKX₂KDE (SEQ ID NO: 21), wherein X₁is lysine and X₂is glutamic acid, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of NLKQX₁IKHVVKX₂KDE (SEQ ID NO: 21), wherein X₁is lysine and X₂is glutamic acid, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise NLKX₁KIKHVVX₂LKDE (SEQ ID NO: 20), wherein X₁is ornithine and X₂is L-2-aminoadipic acid, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of NLKX₁KIKHVVX₂LKDE (SEQ ID NO: 20), wherein X₁is ornithine and X₂is L-2-aminoadipic acid, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise NLKQX₁IKHVVKX₂KDE (SEQ ID NO: 21), wherein X₁is ornithine and X₂is L-2-aminoadipic acid, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of NLKQX₁IKHVVKX₂KDE (SEQ ID NO: 21), wherein X₁is ornithine and X₂is L-2-aminoadipic acid, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise NLKX₁KIKHVVX₂LKDE (SEQ ID NO: 20), wherein X₁is L-2-aminoadipic acid and X₂is ornithine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of NLKX₁KIKHVVX₂LKDE (SEQ ID NO: 20), wherein X₁is L-2-aminoadipic acid and X₂is ornithine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise NLKQX₁IKHVVKX₂KDE (SEQ ID NO: 21), wherein X₁is L-2-aminoadipic acid and X₂is ornithine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of NLKQX₁IKHVVKX₂KDE (SEQ ID NO: 21), wherein X₁is L-2-aminoadipic acid and X₂is ornithine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise NLKX₁KIKHVVX₂LKDE (SEQ ID NO: 20), wherein X₁is alanine derivative R8 and X₂is alanine derivative S5, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of NLKX₁KIKHVVX₂LKDE (SEQ ID NO: 20), wherein X₁is alanine derivative R8 and X₂is alanine derivative S5, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise NLKQX₁IKHVVKX₂KDE (SEQ ID NO: 21), wherein X₁is alanine derivative R8 and X₂is alanine derivative S5, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of NLKQX₁IKHVVKX₂KDE (SEQ ID NO: 21), wherein X₁is alanine derivative R8 and X₂is alanine derivative S5, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise KSEVSKLRX₁QLVKRKX₂NELR (SEQ ID NO: 11), wherein X₁is glutamic acid and X₂is lysine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of KSEVSKLRX₁QLVKRKX₂NELR (SEQ ID NO: 11), wherein X₁is glutamic acid and X₂is lysine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise KSEVSKLRSX₁LVKRKQX₂ELR (SEQ ID NO: 12), wherein X₁is glutamic acid and X₂is lysine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of KSEVSKLRSX₁LVKRKQX₂ELR (SEQ ID NO: 12), wherein X₁is glutamic acid and X₂is lysine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise KSEVSKLRSQX₁VKRKQNX₂LR (SEQ ID NO: 13), wherein X₁is glutamic acid and X₂is lysine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of KSEVSKLRSQX₁VKRKQNX₂LR (SEQ ID NO: 13), wherein X₁is glutamic acid and X₂is lysine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise KSEVSKLRX₁QLVKRKX₂NELR (SEQ ID NO: 11), wherein X₁is lysine and X₂is glutamic acid, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of KSEVSKLRX₁QLVKRKX₂NELR (SEQ ID NO: 11), wherein X₁is lysine and X₂is glutamic acid, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise KSEVSKLRSX₁LVKRKQX₂ELR (SEQ ID NO: 12), wherein X₁is lysine and X₂is glutamic acid, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of KSEVSKLRSX₁LVKRKQX₂ELR (SEQ ID NO: 12), wherein X₁is lysine and X₂is glutamic acid, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise KSEVSKLRSQX₁VKRKQNX₂LR (SEQ ID NO: 13), wherein X₁is lysine and X₂is glutamic acid, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of KSEVSKLRSQX₁VKRKQNX₂LR (SEQ ID NO: 13), wherein X₁is lysine and X₂is glutamic acid, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise KSEVSKLRX₁QLVKRKX₂NELR (SEQ ID NO: 11), wherein X₁is ornithine and X₂is L-2-aminoadipic acid, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of KSEVSKLRX₁QLVKRKX₂NELR (SEQ ID NO: 11), wherein X₁is ornithine and X₂is L-2-aminoadipic acid, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise KSEVSKLRSX₁LVKRKQX₂ELR (SEQ ID NO: 12), wherein X₁is ornithine and X₂is L-2-aminoadipic acid, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of KSEVSKLRSX₁LVKRKQX₂ELR (SEQ ID NO: 12), wherein X₁is ornithine and X₂is L-2-aminoadipic acid, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise KSEVSKLRSQX₁VKRKQNX₂LR (SEQ ID NO: 13), wherein X₁is ornithine and X₂is L-2-aminoadipic acid, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of KSEVSKLRSQX₁VKRKQNX₂LR (SEQ ID NO: 13), wherein X₁is ornithine and X₂is L-2-aminoadipic acid, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise KSEVSKLRX₁QLVKRKX₂NELR (SEQ ID NO: 11), wherein X₁is L-2-aminoadipic acid and X₂is ornithine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of KSEVSKLRX₁QLVKRKX₂NELR (SEQ ID NO: 11), wherein X₁is L-2-aminoadipic acid and X₂is ornithine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise KSEVSKLRSX₁LVKRKQX₂ELR (SEQ ID NO: 12), wherein X₁is L-2-aminoadipic acid and X₂is ornithine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of KSEVSKLRSX₁LVKRKQX₂ELR (SEQ ID NO: 12), wherein X₁is L-2-aminoadipic acid and X₂is ornithine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise KSEVSKLRSQX₁VKRKQNX₂LR (SEQ ID NO: 13), wherein X₁is L-2-aminoadipic acid and X₂is ornithine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of KSEVSKLRSQX₁VKRKQNX₂LR (SEQ ID NO: 13), wherein X₁is L-2-aminoadipic acid and X₂is ornithine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise KSEVSKLRX₁QLVKRKX₂NELR (SEQ ID NO: 11), wherein X₁is alanine derivative R8 and X₂is alanine derivative S5, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of KSEVSKLRX₁QLVKRKX₂NELR (SEQ ID NO: 11), wherein X₁is alanine derivative R8 and X₂is alanine derivative S5, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise KSEVSKLRSX₁LVKRKQX₂ELR (SEQ ID NO: 12), wherein X₁is alanine derivative R8 and X₂is alanine derivative S5, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of KSEVSKLRSX₁LVKRKQX₂ELR (SEQ ID NO: 12), wherein X₁is alanine derivative R8 and X₂is alanine derivative S5, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise KSEVSKLRSQX₁VKRKQNX₂LR (SEQ ID NO: 13), wherein X₁is alanine derivative R8 and X₂is alanine derivative S5, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of KSEVSKLRSQX₁VKRKQNX₂LR (SEQ ID NO: 13), wherein X₁is alanine derivative R8 and X₂is alanine derivative S5, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise KIKHVVKLKX₁ENSQLKX₂EVSKLRSQLVKRK (SEQ ID NO: 22), wherein X₁is glutamic acid and X₂is lysine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of KIKHVVKLKX₁ENSQLKX₂EVSKLRSQLVKRK (SEQ ID NO: 22), wherein X₁is glutamic acid and X₂is lysine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise KIKHVVKLKDX₁NSQLKSX₂VSKLRSQLVKRK (SEQ ID NO: 23), wherein X₁is glutamic acid and X₂is lysine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of KIKHVVKLKDX₁NSQLKSX₂VSKLRSQLVKRK (SEQ ID NO: 23), wherein X₁is glutamic acid and X₂is lysine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise KIKHVVKLKDEX₁SQLKSEX₂SKLRSQLVKRK (SEQ ID NO: 24), wherein X₁is glutamic acid and X₂is lysine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of KIKHVVKLKDEX₁SQLKSEX₂SKLRSQLVKRK (SEQ ID NO: 24), wherein X₁is glutamic acid and X₂is lysine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise KIKHVVKLKDENX₁QLKSEVX₂KLRSQLVKRK (SEQ ID NO: 25), wherein X₁is glutamic acid and X₂is lysine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of KIKHVVKLKDENX₁QLKSEVX₂KLRSQLVKRK (SEQ ID NO: 25), wherein X₁is glutamic acid and X₂is lysine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise KIKHVVKLKX₁ENSQLKX₂EVSKLRSQLVKRK (SEQ ID NO: 22), wherein X₁is lysine and X₂is glutamic acid, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of KIKHVVKLKX₁ENSQLKX₂EVSKLRSQLVKRK (SEQ ID NO: 22), wherein X₁is lysine and X₂is glutamic acid, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise KIKHVVKLKDX₁NSQLKSX₂VSKLRSQLVKRK (SEQ ID NO: 23), wherein X₁is lysine and X₂is glutamic acid, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of KIKHVVKLKDX₁NSQLKSX₂VSKLRSQLVKRK (SEQ ID NO: 23), wherein X₁is lysine and X₂is glutamic acid, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise KIKHVVKLKDEX₁SQLKSEX₂SKLRSQLVKRK (SEQ ID NO: 24), wherein X₁is lysine and X₂is glutamic acid, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of KIKHVVKLKDEX₁SQLKSEX₂SKLRSQLVKRK (SEQ ID NO: 24), wherein X₁is lysine and X₂is glutamic acid, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise KIKHVVKLKDENX₁QLKSEVX₂KLRSQLVKRK (SEQ ID NO: 25), wherein X₁is lysine and X₂is glutamic acid, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of KIKHVVKLKDENX₁QLKSEVX₂KLRSQLVKRK (SEQ ID NO: 25), wherein X₁is lysine and X₂is glutamic acid, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise KIKHVVKLKX₁ENSQLKX₂EVSKLRSQLVKRK (SEQ ID NO: 22), wherein X₁is ornithine and X₂is L-2-aminoadipic acid, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of KIKHVVKLKX₁ENSQLKX₂EVSKLRSQLVKRK (SEQ ID NO: 22), wherein X₁is ornithine and X₂is L-2-aminoadipic acid, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise KIKHVVKLKDX₁NSQLKSX₂VSKLRSQLVKRK (SEQ ID NO: 23), wherein X₁is ornithine and X₂is L-2-aminoadipic acid, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of KIKHVVKLKDX₁NSQLKSX₂VSKLRSQLVKRK (SEQ ID NO: 23), wherein X₁is ornithine and X₂is L-2-aminoadipic acid, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise KIKHVVKLKDEX₁SQLKSEX₂SKLRSQLVKRK (SEQ ID NO: 24), wherein X₁is ornithine and X₂is L-2-aminoadipic acid, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of KIKHVVKLKDEX₁SQLKSEX₂SKLRSQLVKRK (SEQ ID NO: 24), wherein X₁is ornithine and X₂is L-2-aminoadipic acid, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise KIKHVVKLKDENX₁QLKSEVX₂KLRSQLVKRK (SEQ ID NO: 25), wherein X₁is ornithine and X₂is L-2-aminoadipic acid, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of KIKHVVKLKDENX₁QLKSEVX₂KLRSQLVKRK (SEQ ID NO: 25), wherein X₁is ornithine and X₂is L-2-aminoadipic acid, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise KIKHVVKLKX₁ENSQLKX₂EVSKLRSQLVKRK (SEQ ID NO: 22), wherein X₁is L-2-aminoadipic acid and X₂is ornithine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of KIKHVVKLKX₁ENSQLKX₂EVSKLRSQLVKRK (SEQ ID NO: 22), wherein X₁is L-2-aminoadipic acid and X₂is ornithine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise KIKHVVKLKDX₁NSQLKSX₂VSKLRSQLVKRK (SEQ ID NO: 23), wherein X₁is L-2-aminoadipic acid and X₂is ornithine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of KIKHVVKLKDX₁NSQLKSX₂VSKLRSQLVKRK (SEQ ID NO: 23), wherein X₁is L-2-aminoadipic acid and X₂is ornithine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise KIKHVVKLKDEX₁SQLKSEX₂SKLRSQLVKRK (SEQ ID NO: 24), wherein X₁is L-2-aminoadipic acid and X₂is ornithine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of KIKHVVKLKDEX₁SQLKSEX₂SKLRSQLVKRK (SEQ ID NO: 24), wherein X₁is L-2-aminoadipic acid and X₂is ornithine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise KIKHVVKLKDENX₁QLKSEVX₂KLRSQLVKRK (SEQ ID NO: 25), wherein X₁is L-2-aminoadipic acid and X₂is ornithine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of KIKHVVKLKDENX₁QLKSEVX₂KLRSQLVKRK (SEQ ID NO: 25), wherein X₁is L-2-aminoadipic acid and X₂is ornithine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise KIKHVVKLKX₁ENSQLKX₂EVSKLRSQLVKRK (SEQ ID NO: 22), wherein X₁is alanine derivative R8 and X₂is alanine derivative S5, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of KIKHVVKLKX₁ENSQLKX₂EVSKLRSQLVKRK (SEQ ID NO: 22), wherein X₁is alanine derivative R8 and X₂is alanine derivative S5, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise KIKHVVKLKDX₁NSQLKSX₂VSKLRSQLVKRK (SEQ ID NO: 23), wherein X₁is alanine derivative R8 and X₂is alanine derivative S5, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of KIKHVVKLKDX₁NSQLKSX₂VSKLRSQLVKRK (SEQ ID NO: 23), wherein X₁is alanine derivative R8 and X₂is alanine derivative S5, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise KIKHVVKLKDEX₁SQLKSEX₂SKLRSQLVKRK (SEQ ID NO: 24), wherein X₁is alanine derivative R8 and X₂is alanine derivative S5, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of KIKHVVKLKDEX₁SQLKSEX₂SKLRSQLVKRK (SEQ ID NO: 24), wherein X₁is alanine derivative R8 and X₂is alanine derivative S5, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise KIKHVVKLKDENX₁QLKSEVX₂KLRSQLVKRK (SEQ ID NO: 25), wherein X₁is alanine derivative R8 and X₂is alanine derivative S5, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of KIKHVVKLKDENX₁QLKSEVX₂KLRSQLVKRK (SEQ ID NO: 25), wherein X₁is alanine derivative R8 and X₂is alanine derivative S5, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise KIKHVVKLKX₁ENSX₂X₃KSEX₄SKLRSQLVKRK (SEQ ID NO: 26), wherein X₁is glutamic acid, X₂is lysine, X₃is glutamic acid, X₄is lysine, and wherein X₁is covalently bonded to X₂and X₃is covalently bonded to X₄.

The amino acid sequence of the peptide can consist of KIKHVVKLKX₁ENSX₂X₃KSEX₄SKLRSQLVKRK (SEQ ID NO: 26), wherein X₁is glutamic acid, X₂is lysine, X₃is glutamic acid, X₄is lysine, and wherein X₁is covalently bonded to X₂and X₃is covalently bonded to X₄.

The amino acid sequence of the peptide can comprise KIKHVVKLKDX₁NSQX₂X₃SEVX₄KLRSQLVKRK (SEQ ID NO: 27), wherein X₁is glutamic acid, X₂is lysine, X₃is glutamic acid, X₄is lysine, and wherein X₁is covalently bonded to X₂and X₃is covalently bonded to X₄.

The amino acid sequence of the peptide can consist of KIKHVVKLKDX₁NSQX₂X₃SEVX₄KLRSQLVKRK (SEQ ID NO: 27), wherein X₁is glutamic acid, X₂is lysine, X₃is glutamic acid, X₄is lysine, and wherein X₁is covalently bonded to X₂and X₃is covalently bonded to X₄.

The amino acid sequence of the peptide can comprise KIKHVVKLKX₁ENSX₂X₃KSEX₄SKLRSQLVKRK (SEQ ID NO: 26), wherein X₁is lysine, X₂is glutamic acid, X₃is lysine, X₄is glutamic acid, and wherein X₁is covalently bonded to X₂and X₃is covalently bonded to X₄.

The amino acid sequence of the peptide can consist of KIKHVVKLKX₁ENSX₂X₃KSEX₄SKLRSQLVKRK (SEQ ID NO: 26), wherein X₁is lysine, X₂is glutamic acid, X₃is lysine, X₄is glutamic acid, and wherein X₁is covalently bonded to X₂and X₃is covalently bonded to X₄.

The amino acid sequence of the peptide can comprise KIKHVVKLKDX₁NSQX₂X₃SEVX₄KLRSQLVKRK (SEQ ID NO: 27), wherein X₁is lysine, X₂is glutamic acid, X₃is lysine, X₄is glutamic acid, and wherein X₁is covalently bonded to X₂and X₃is covalently bonded to X₄.

The amino acid sequence of the peptide can consist of IKHVVKLKDX₁NSQX₂X₃SEVX₄KLRSQLVKRK (SEQ ID NO: 27), wherein X₁is lysine, X₂is glutamic acid, X₃is lysine, X₄is glutamic acid, and wherein X₁is covalently bonded to X₂and X₃is covalently bonded to X₄.

The amino acid sequence of the peptide can comprise KIKHVVKLKX₁ENSX₂X₃KSEX₄SKLRSQLVKRK (SEQ ID NO: 26), wherein X₁is glutamic acid, X₂is lysine, X₃is lysine, X₄is glutamic acid, and wherein X₁is covalently bonded to X₂and X₃is covalently bonded to X₄.

The amino acid sequence of the peptide can consist of KIKHVVKLKX₁ENSX₂X₃KSEX₄SKLRSQLVKRK (SEQ ID NO: 26), wherein X₁is glutamic acid, X₂is lysine, X₃is lysine, X₄is glutamic acid, and wherein X₁is covalently bonded to X₂and X₃is covalently bonded to X₄.

The amino acid sequence of the peptide can comprise KIKHVVKLKDX₁NSQX₂X₃SEVX₄KLRSQLVKRK (SEQ ID NO: 27), wherein X₁is glutamic acid, X₂is lysine, X₃is lysine, X₄is glutamic acid, and wherein X₁is covalently bonded to X₂and X₃is covalently bonded to X₄.

The amino acid sequence of the peptide can consist of KIKHVVKLKDX₁NSQX₂X₃SEVX₄KLRSQLVKRK (SEQ ID NO: 27), wherein X₁is glutamic acid, X₂is lysine, X₃is lysine, X₄is glutamic acid, and wherein X₁is covalently bonded to X₂and X₃is covalently bonded to X₄.

The amino acid sequence of the peptide can comprise KIKHVVKLKX₁ENSX₂X₃KSEX₄SKLRSQLVKRK (SEQ ID NO: 26), wherein X₁is lysine, X₂is glutamic acid, X₃is glutamic acid, X₄is lysine, and wherein X₁is covalently bonded to X₂and X₃is covalently bonded to X₄.

The amino acid sequence of the peptide can consist of KIKHVVKLKX₁ENSX₂X₃KSEX₄SKLRSQLVKRK (SEQ ID NO: 26), wherein X₁is lysine, X₂is glutamic acid, X₃is glutamic acid, X₄is lysine, and wherein X₁is covalently bonded to X₂and X₃is covalently bonded to X₄.

The amino acid sequence of the peptide can comprise KIKHVVKLKDX₁NSQX₂X₃SEVX₄KLRSQLVKRK (SEQ ID NO: 27), wherein X₁is lysine, X₂is glutamic acid, X₃is glutamic acid, X₄is lysine, and wherein X₁is covalently bonded to X₂and X₃is covalently bonded to X₄.

The amino acid sequence of the peptide can consist of KIKHVVKLKDX₁NSQX₂X₃SEVX₄KLRSQLVKRK (SEQ ID NO: 27), wherein X₁is lysine, X₂is glutamic acid, X₃is glutamic acid, X₄is lysine, and wherein X₁is covalently bonded to X₂and X₃is covalently bonded to X₄.

The amino acid sequence of the peptide can comprise KIKHVVKLKX₁ENSX₂X₃KSEX₄SKLRSQLVKRK (SEQ ID NO: 26), wherein X₁is ornithine, X₂is L-2-aminoadipic acid, X₃is ornithine, X₄is L-2-aminoadipic acid, and wherein X₁is covalently bonded to X₂and X₃is covalently bonded to X₄.

The amino acid sequence of the peptide can consist of KIKHVVKLKX₁ENSX₂X₃KSEX₄SKLRSQLVKRK (SEQ ID NO: 26), wherein X₁is ornithine, X₂is L-2-aminoadipic acid, X₃is ornithine, X₄is L-2-aminoadipic acid, and wherein X₁is covalently bonded to X₂and X₃is covalently bonded to X₄.

The amino acid sequence of the peptide can comprise KIKHVVKLKDX₁NSQX₂X₃SEVX₄KLRSQLVKRK (SEQ ID NO: 27), wherein X₁is ornithine, X₂is L-2-aminoadipic acid, X₃is ornithine, X₄is L-2-aminoadipic acid, and wherein X₁is covalently bonded to X₂and X₃is covalently bonded to X₄.

The amino acid sequence of the peptide can consist of KIKHVVKLKDX₁NSQX₂X₃SEVX₄KLRSQLVKRK (SEQ ID NO: 27), wherein X₁is ornithine, X₂is L-2-aminoadipic acid, X₃is ornithine, X₄is L-2-aminoadipic acid, and wherein X₁is covalently bonded to X₂and X₃is covalently bonded to X₄.

The amino acid sequence of the peptide can comprise KIKHVVKLKX₁ENSX₂X₃KSEX₄SKLRSQLVKRK (SEQ ID NO: 26), wherein X₁is L-2-aminoadipic acid, X₂is ornithine, X₃is L-2-aminoadipic acid, X₄is ornithine, and wherein X₁is covalently bonded to X₂and X₃is covalently bonded to X₄.

The amino acid sequence of the peptide can consist of KIKHVVKLKX₁ENSX₂X₃KSEX₄SKLRSQLVKRK (SEQ ID NO: 26), wherein X₁is L-2-aminoadipic acid, X₂is ornithine, X₃is L-2-aminoadipic acid, X₄is ornithine, and wherein X₁is covalently bonded to X₂and X₃is covalently bonded to X₄.

The amino acid sequence of the peptide can comprise KIKHVVKLKDX₁NSQX₂X₃SEVX₄KLRSQLVKRK (SEQ ID NO: 27), wherein X₁is L-2-aminoadipic acid, X₂is ornithine, X₃is L-2-aminoadipic acid, X₄is ornithine, and wherein X₁is covalently bonded to X₂and X₃is covalently bonded to X₄.

The amino acid sequence of the peptide can consist of KIKHVVKLKDX₁NSQX₂X₃SEVX₄KLRSQLVKRK (SEQ ID NO: 27), wherein X₁is L-2-aminoadipic acid, X₂is ornithine, X₃is L-2-aminoadipic acid, X₄is ornithine, and wherein X₁is covalently bonded to X₂and X₃is covalently bonded to X₄.

The amino acid sequence of the peptide can comprise KIKHVVKLKX₁ENSX₂X₃KSEX₄SKLRSQLVKRK (SEQ ID NO: 26), wherein X₁is ornithine, X₂is L-2-aminoadipic acid, X₃is L-2-aminoadipic acid, X₄is ornithine, and wherein X₁is covalently bonded to X₂and X₃is covalently bonded to X₄.

The amino acid sequence of the peptide can consist of KIKHVVKLKX₁ENSX₂X₃KSEX₄SKLRSQLVKRK (SEQ ID NO: 26), wherein X₁is ornithine, X₂is L-2-aminoadipic acid, X₃is L-2-aminoadipic acid, X₄is ornithine, and wherein X₁is covalently bonded to X₂and X₃is covalently bonded to X₄.

The amino acid sequence of the peptide can comprise KIKHVVKLKDX₁NSQX₂X₃SEVX₄KLRSQLVKRK (SEQ ID NO: 27), wherein X₁is ornithine, X₂is L-2-aminoadipic acid, X₃is L-2-aminoadipic acid, X₄is ornithine, and wherein X₁is covalently bonded to X₂and X₃is covalently bonded to X₄.

The amino acid sequence of the peptide can consist of KIKHVVKLKDX₁NSQX₂X₃SEVX₄KLRSQLVKRK (SEQ ID NO: 27), wherein X₁is ornithine, X₂is L-2-aminoadipic acid, X₃is L-2-aminoadipic acid, X₄is ornithine, and wherein X₁is covalently bonded to X₂and X₃is covalently bonded to X₄.

The amino acid sequence of the peptide can comprise KIKHVVKLKX₁ENSX₂X₃KSEX₄SKLRSQLVKRK (SEQ ID NO: 26), wherein X₁is L-2-aminoadipic acid, X₂is ornithine, X₃is ornithine, X₄is L-2-aminoadipic acid, and wherein X₁is covalently bonded to X₂and X₃is covalently bonded to X₄.

The amino acid sequence of the peptide can consist of KIKHVVKLKX₁ENSX₂X₃KSEX₄SKLRSQLVKRK (SEQ ID NO: 26), wherein X₁is L-2-aminoadipic acid, X₂is ornithine, X₃is ornithine, X₄is L-2-aminoadipic acid, and wherein X₁is covalently bonded to X₂and X₃is covalently bonded to X₄.

The amino acid sequence of the peptide can comprise KIKHVVKLKDX₁NSQX₂X₃SEVX₄KLRSQLVKRK (SEQ ID NO: 27), wherein X₁is L-2-aminoadipic acid, X₂is ornithine, X₃is ornithine, X₄is L-2-aminoadipic acid, and wherein X₁is covalently bonded to X₂and X₃is covalently bonded to X₄.

The amino acid sequence of the peptide can consist of KIKHVVKLKDX₁NSQX₂X₃SEVX₄KLRSQLVKRK (SEQ ID NO: 27), wherein X₁is L-2-aminoadipic acid, X₂is ornithine, X₃is ornithine, X₄is L-2-aminoadipic acid, and wherein X₁is covalently bonded to X₂and X₃is covalently bonded to X₄.

The amino acid sequence of the peptide can comprise KIKHVVKLKX₁ENSX₂X₃KSEX₄SKLRSQLVKRK (SEQ ID NO: 26), wherein X₁, X₂, X₃, and X₄are each allylglycine, and wherein X₁is covalently bonded to X₂and X₃is covalently bonded to X₄.

The amino acid sequence of the peptide can consist of KIKHVVKLKX₁ENSX₂X₃KSEX₄SKLRSQLVKRK (SEQ ID NO: 26), wherein X₁, X₂, X₃, and X₄are each allylglycine, and wherein X₁is covalently bonded to X₂and X₃is covalently bonded to X₄.

The amino acid sequence of the peptide can comprise KIKHVVKLKDX₁NSQX₂X₃SEVX₄KLRSQLVKRK (SEQ ID NO: 27), wherein X₁, X₂, X₃, and X₄are each allylglycine, and wherein X₁is covalently bonded to X₂and X₃is covalently bonded to X₄.

The amino acid sequence of the peptide can consist of KIKHVVKLKDX₁NSQX₂X₃SEVX₄KLRSQLVKRK (SEQ ID NO: 27), wherein X₁, X₂, X₃, and X₄are each allylglycine, and wherein X₁is covalently bonded to X₂and X₃is covalently bonded to X₄.

The amino acid sequence of the peptide can comprise KIKHVVKLKX₁ENSX₂X₃KSEX₄SKLRSQLVKRK (SEQ ID NO: 26), wherein X₁, X₂, X₃, and X₄are each alanine derivative S5, and wherein X₁is covalently bonded to X₂and X₃is covalently bonded to X₄.

The amino acid sequence of the peptide can consist of KIKHVVKLKX₁ENSX₂X₃KSEX₄SKLRSQLVKRK (SEQ ID NO: 26), wherein X₁, X₂, X₃, and X₄are each alanine derivative S5, and wherein X₁is covalently bonded to X₂and X₃is covalently bonded to X₄.

The amino acid sequence of the peptide can comprise KIKHVVKLKDX₁NSQX₂X₃SEVX₄KLRSQLVKRK (SEQ ID NO: 27), wherein X₁, X₂, X₃, and X₄are each alanine derivative S5, and wherein X₁is covalently bonded to X₂and X₃is covalently bonded to X₄.

The amino acid sequence of the peptide can consist of KIKHVVKLKDX₁NSQX₂X₃SEVX₄KLRSQLVKRK (SEQ ID NO: 27), wherein X₁, X₂, X₃, and X₄are each alanine derivative S5, and wherein X₁is covalently bonded to X₂and X₃is covalently bonded to X₄.

The amino acid sequence of the peptide can comprise NLKQKIKHVVKLKDENSQLKSEVSKLRX₁QLVX₂RKQN (SEQ ID NO: 28), wherein X₁is glutamic acid and X₂is lysine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of NLKQKIKHVVKLKDENSQLKSEVSKLRX₁QLVX₂RKQN (SEQ ID NO: 28), wherein X₁is glutamic acid and X₂is lysine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise NLKQKIX₁HVVX₂LKDENSQLKSEVSKLRX₃QLVX₄RKQN (SEQ ID NO: 29), wherein X₁is glutamic acid, X₂is lysine, X₃is glutamic acid, X₄is lysine, and wherein X₁is covalently bonded to X₂and X₃is covalently bonded to X₄.

The amino acid sequence of the peptide can consist of NLKQKIX₁HVVX₂LKDENSQLKSEVSKLRX₃QLVX₄RKQN (SEQ ID NO: 29), wherein X₁is glutamic acid, X₂is lysine, X₃is glutamic acid, X₄is lysine, and wherein X₁is covalently bonded to X₂and X₃is covalently bonded to X₄.

The amino acid sequence of the peptide can comprise NLKQKIKHVVKLKDENSQLKSEVSKLX₁SQLX₂KRKQN (SEQ ID NO: 30), wherein X₁is glutamic acid and X₂is lysine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of NLKQKIKHVVKLKDENSQLKSEVSKLX₁SQLX₂KRKQN (SEQ ID NO: 30), wherein X₁is glutamic acid and X₂is lysine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise NLKQKIX₁HVVX₂LKDENSQLKSEVSKLRSQLVKRKQN (SEQ ID NO: 31), wherein X₁is glutamic acid and X₂is lysine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can consist of NLKQKIX₁HVVX₂LKDENSQLKSEVSKLRSQLVKRKQN (SEQ ID NO: 31), wherein X₁is glutamic acid and X₂is lysine, and wherein X₁is covalently bonded to X₂.

The amino acid sequence of the peptide can comprise LKQKIX₁HVVX₂LKDENSQLKSEVSKLX₃SQLX₄KRKQN (SEQ ID NO: 32), wherein X₁is glutamic acid, X₂is lysine, X₃is glutamic acid, X₄is lysine, and wherein X₁is covalently bonded to X₂and X₃is covalently bonded to X₄.

The amino acid sequence of the peptide can consist of LKQKIX₁HVVX₂LKDENSQLKSEVSKLX₃SQLX₄KRKQN (SEQ ID NO: 32), wherein X₁is glutamic acid, X₂is lysine, X₃is glutamic acid, X₄is lysine, and wherein X₁is covalently bonded to X₂and X₃is covalently bonded to X₄.

For example, the amino acid sequence of the peptide can comprise or consist of:

VSKX₁RSQX₂VKRKQN (SEQ ID NO: 7), wherein X₁is glutamic acid and X₂is lysine, and wherein X₁is covalently bonded to X₂;

VSKLX₁SQLX₂KRKQN (SEQ ID NO: 8), wherein X₁is glutamic acid and X₂is lysine, and wherein X₁is covalently bonded to X₂;

VSKLRX₁QLVX₂RKQN (SEQ ID NO: 9), wherein X₁is glutamic acid and X₂is lysine, and wherein X₁is covalently bonded to X₂;

VSKLRSX₁LVKX₂KQN (SEQ ID NO: 10), wherein X₁is glutamic acid and X₂is lysine, and wherein X₁is covalently bonded to X₂;

VSKLX₁SQLX₂KRKQN (SEQ ID NO: 8), wherein X₁is lysine and X₂is glutamic acid, and wherein X₁is covalently bonded to X₂;

VSKLRX₁QLVX₂RKQN (SEQ ID NO: 9), wherein X₁is lysine and X₂is glutamic acid, and wherein X₁is covalently bonded to X₂;

NLKX₁KIKX₂VVKLKDE (SEQ ID NO: 15), wherein X₁is glutamic acid and X₂is lysine, and wherein X₁is covalently bonded to X₂;

NLKQX₁IKHX₂VKLKDE (SEQ ID NO: 16), wherein X₁is glutamic acid and X₂is lysine, and wherein X₁is covalently bonded to X₂;

NLKQKX₁KHVX₂KLKDE (SEQ ID NO: 17), wherein X₁is glutamic acid and X₂is lysine, and wherein X₁is covalently bonded to X₂;

NLKQKIX₁HVVX₂LKDE (SEQ ID NO: 18), wherein X₁is glutamic acid and X₂is lysine, and wherein X₁is covalently bonded to X₂;

NLKQKIKX₁VVKX₂KDE (SEQ ID NO: 19), wherein X₁is glutamic acid and X₂is lysine, and wherein X₁is covalently bonded to X₂;

KIKHVVKLKX₁ENSX₂X₃KSEX₄SKLRSQLVKRK (SEQ ID NO: 26), wherein X₁is glutamic acid, X₂is lysine, X₃is glutamic acid, X₄is lysine, and wherein X₁is covalently bonded to X₂and X₃is covalently bonded to X₄;

KIKHVVKLKDX₁NSQX₂X₃SEVX₄KLRSQLVKRK (SEQ ID NO: 27), wherein X₁is glutamic acid, X₂is lysine, X₃is glutamic acid, X₄is lysine, and wherein X₁is covalently bonded to X₂and X₃is covalently bonded to X₄;

KIKHVVKLKX₁ENSX₂X₃KSEX₄SKLRSQLVKRK (SEQ ID NO: 26), wherein X₁is glutamic acid, X₂is lysine, X₃is lysine, X₄is glutamic acid, and wherein X₁is covalently bonded to X₂and X₃is covalently bonded to X₄;

KIKHVVKLKX₁ENSX₂X₃KSEX₄SKLRSQLVKRK (SEQ ID NO: 26), wherein X₁is lysine, X₂is glutamic acid, X₃is glutamic acid, X₄is lysine, and wherein X₁is covalently bonded to X₂and X₃is covalently bonded to X₄;

NLKQKIKHVVKLKDENSQLKSEVSKLRX₁QLVX₂RKQN (SEQ ID NO: 28), wherein X₁is glutamic acid and X₂is lysine, and wherein X₁is covalently bonded to X₂; or

NLKQKIX₁HVVX₂LKDENSQLKSEVSKLRX₃QLVX₄RKQN (SEQ ID NO: 29), wherein X₁is glutamic acid, X₂is lysine, X₃is glutamic acid, X₄is lysine, and wherein X₁is covalently bonded to X₂and X₃is covalently bonded to X₄.

The amino acid sequence of the peptide can comprise or consist of: