Pompilid wasp-derived neuropeptides

Abstract

The present invention provides a peptide represented by the amino acid sequence formula (A):H-X1-X2-X3-X4-Gly-X6-X7-Asp-Gln-R  (A)wherein:each of X1 and X3 independently represents Arg or Lys, each of X2, X4 and X6 independently represents Ile or Leu, and X7 represents Phe, Tyr or Trp; andR represents -NH2, -Leu-NH2, -Leu-Ser-NH2, -Leu-Ser-Lys-NH2, -Leu-Ser-Arg-NH2, -Leu-Ser-Lys-Leu-NH2, or -Leu-Ser-Arg-Leu-NH2;and a salt thereof.(In the above, Gly stands for a glycine residue, Asp stands for an aspartic acid residue, Gln stands for a glutamine residue, Arg stands for an arginine residue, Lys stands for a lysine residue, Ile stands for an isoleucine residue, Leu stands for a leucine residue, Phe stands for a phenylalanine residue, Tyr stands for a tyrosine residue, Trp stands for a tryptophan residue, and Ser stands for a serine residue.)The peptide acts on glutamate receptors and is expected to be useful in the treatment of cerebral nerve diseases associated with glutamic acid.

Description

This application is a 371 of PCT/JP98/03730, filed Aug. 24, 1998, which claims the priority of Japan JP9-241699, filed Aug. 25, 1997

TECHNICAL FIELD

The present invention relates to novel neuropeptides and more specifically to peptides obtained from the venoms of the solitary wasps Anoplius samariensis and Batozonellus maculifrons , and analogous peptides thereof.

BACKGROUND ART

Since solitary wasp species such as thread-waisted wasps and pompilid wasps paralyze other insects with their venom, it is believed that the venom contain substances that act on the nervous system. In fact, peptides called mastoparans have been isolated from a certain kind of solitary wasp, and these peptides are used as useful compounds for the study of information transmission system of the living body.

On the other hand, various compounds have been isolated in the studies on spider toxins, and it has been confirmed that their effect of paralyzing nerves is based on their inhibitory action on glutamate receptors. Glutamic acid is known to play an important role as an excitatory neurotransmitter mediated by glutamate receptors in the central nervous system (e.g. brain, spinal cord) of mammals, and the synapses of insects and crustaceans. And further, it is known that excess glutamic acid causes over-excitation of nerve cells resulting in death of the nerve cells. Therefore, enhancement of the function of glutamate receptors and conversely temporary blocking of their function are believed to provide therapeutic benefits on cerebral nerve diseases associated with glutamic acid.

DISCLOSURE OF THE INVENTION

Accordingly, the object of the present invention is to find, in the venom of the solitary wasps, substances that act on the glutamate receptor or substances that promote or inhibit the release of glutamic acid, and to apply them to medical therapeutic purposes.

In order to achieve the above object, the present inventors have isolated a peptide (1) represented by SEQ ID NO: 1:

H-Arg-Ile-Lys-Ile-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Lys-Leu-NH 2   (1)

and a peptide (97) represented by SEQ ID NO: 2:

H-Arg-Ile-Lys-Ile-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Arg-Leu-NH 2   (97)

from the venom sac extracts of solitary wasps A. samariensis and B. maculifrons , on the basis of the ability to enhance or block the neurotransmission through the neuron synapses of lobster's walking leg.

Furthermore, peptides related to the above peptides (1) and (97) were synthesized by the conventional solid phase method and their structure-activity relationship was examined. As a result, it was found that the peptides represented by the amino acid sequence formula (A):

H-X 1 -X 2 -X 3 -X 4 -Gly-X 6 -X 7 -Asp-Gln-R  (A)

wherein:

R is basically NH 2, which also may be -Leu-NH 2 , -Leu-Ser-NH 2 , -Leu-Ser-Lys-NH 2 , -Leu-Ser-Arg-NH 2 , -Leu-Ser-Lys-Leu-NH 2 , (SEQ ID NO:3) or -Leu-Ser-Arg-Leu-NH 2 (SEQ ID NO:4),

X 1 and X 3 are basic amino acid residues;

X 2 , X 4 and X 6 are aliphatic amino acid residues; and

X 7 is an aromatic amino acid residue, can show the above-mentioned activity.

The basic amino acid residues X 1 and X 3 include arginine or lysine residue, the aliphatic amino acid residues X 2 , X 4 and X 6 include leucine or isoleucine residue, and the aromatic amino acid residue X 7 includes phenylalanine, tyrosine, or tryptophan residue.

Accordingly, the present invention provides, as a neuro-peptide, a peptide represented by the amino acid sequence formula (A):

H-X 1 -X 2 -X 3 -X 4 -Gly-X 6 -X 7 -Asp-Gln-R  (A)

wherein:

each of X 1 and X 3 independently represents Arg or Lys, each of X 2 , X 4 and X 6 independently represents Ile or Leu, and X 7 represents Phe, Tyr or Trp; and

R represents —NH 2 , -Leu-NH 2 , -Leu-Ser-NH 2 , -Leu-Ser-Lys-NH 2 , -Leu-Ser-Arg-NH 2 , -Leu-Ser-Lys-Leu-NH 2 , (SEQ ID NO:3) or -Leu-Ser-Arg-Leu-NH 2 (SEQ ID NO:4);

and a salt thereof.

As an embodiment, the present invention provides a peptide represented by the amino acid sequence formula (B):

H-X 1 -X 2 -X 3 -X 4 -Gly-X 6 -X 7 -Asp-Gln-NH 2   (B)

wherein:

each of X 1 and X 3 independently represents Arg or Lys, each of X 2 , X 4 and X 6 independently represents Ile or Leu, and X 7 represents Phe, Tyr or Trp;

and a salt thereof.

As another embodiment, the present invention provides a peptide represented by the amino acid sequence formula (C):

H-X 1 -X 2 -X 3 -X 4 -Gly-X 6 -X 7 -Asp-Gln-Leu-NH 2 (C)  (SEQ ID NO:200)

wherein:

each of X 1 and X 3 independently represents Arg or Lys, each of X 2 , X 4 and X 6 independently represents Ile or Leu, and X 7 represents Phe, Tyr or Trp;

and a salt thereof.

As a further embodiment, the present invention provides a peptide represented by the amino acid sequence formula (D):

H-X 1 -X 2 -X 3 -X 4 -Gly-X 6 -X 7 -Asp-Gln-Leu-Ser-NH 2 (D)  (SEQ ID NO:199)

wherein:

each of X 1 and X 3 independently represents Arg or Lys, each of X 2 , X 4 and X 6 independently represents Ile or Leu, and X 7 represents Phe, Tyr or Trp;

and a salt thereof.

As still another embodiment, the present invention provides a peptide represented by the amino acid sequence formula (E):

H-X 1 -X 2 -X 3 -X 4 -Gly-X 6 -X 7 -Asp-Gln-Leu-Ser-Lys-NH 2 (E)  (SEQ ID NO:5)

wherein:

each of X 1 and X 3 independently represents Arg or Lys, each of X 2 , X 4 and X 6 independently represents Ile or Leu, and X 7 represents Phe, Tyr or Trp;

and a salt thereof.

As still another embodiment, the present invention provides a peptide represented by the amino acid sequence formula (F):

H-X 1 -X 2 -X 3 -X 4 -Gly-X 6 -X 7 -Asp-Gln-Leu-Ser-Arg-NH 2 (F)  (SEQ ID NO:6)

wherein:

each of X 1 and X 3 independently represents Arg or Lys, each of X 2 , X 4 and X 6 independently represents Ile or Leu, and X 7 represents Phe, Tyr or Trp;

and a salt thereof.

As still another embodiment, the present invention provides a peptide represented by the amino acid sequence formula (G):

H-X 1 -X 2 -X 3 -X 4 -Gly-X 6 -X 7 -Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (G)  (SEQ ID NO:7)

wherein:

each of X 1 and X 3 independently represents Arg or Lys, each of X 2 , X 4 and X 6 independently represents Ile or Leu, and X 7 represents Phe, Tyr or Trp;

and a salt thereof.

As still a further embodiment, the present invention provides a peptide represented by the amino acid sequence formula (H):

H-X 1 -X 2 -X 3 -X 4 -Gly-X 6 -X 7 -Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (H)  (SEQ ID NO:8)

wherein:

each of X 1 and X 3 independently represents Arg or Lys, each of X 2 , X 4 and X 6 independently represents Ile or Leu, and X 7 represents Phe, Tyr or Trp;

and a salt thereof.

Among the above peptides provided by the present invention, the most preferred embodiment is a peptide represented by the amino acid sequence formula (1):

H-Arg-Ile-Lys-Ile-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (1)  (SEQ ID NO:1)

and a salt thereof, or a peptide represented by the amino acid sequence formula (97):

H-Arg-Ile-Lys-Ile-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (97)  (SEQ ID NO:2)

and a salt thereof.

As another embodiment, the present invention provides a pharmaceutical composition containing the peptide represented by the amino acid sequence formula (A) or a salt thereof for treatment of glutamate receptor related diseases.

As still another embodiment, the present invention provides use of the peptide represented by the amino acid sequence formula (A) or a salt thereof for treatment of glutamate receptor related diseases.

As still a further embodiment, the present invention provides a method for treatment of glutamate receptor related diseases which composing administering an effective amount of the peptide represented by the amino acid sequence formula (A) or a salt thereof.

BEST MODE FOR CARRYING OUT THE INVENTION

In the present specification and in each of the above formulae, Gly stands for a glycine residue, Asp stands for an aspartic acid residue, Gln stands for a glutamine residue, Arg stands for an arginine residue, Lys stands for a lysine residue, Ile stands for an isoleucine residue, Leu stands for a leucine residue, Phe stands for a phenylalanine residue, Tyr stands for a tyrosine residue, Trp stands for a tryptophan residue, and Ser stands for a serine residue. Amino acid sequences are indicated by the triplet code of IUPAC.

The peptides provided by the present invention include the following peptides:

H-Arg-Ile-Lys-Ile-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (1) (SEQ ID NO:1)

H-Arg-Ile-Lys-Ile-Gly-Leu-Tyr-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (2) (SEQ ID NO:9)

H-Arg-Ile-Lys-Ile-Gly-Leu-Trp-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (3) (SEQ ID NO:10)

H-Arg-Ile-Lys-Ile-Gly-Ile-Phe-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (4) (SEQ ID NO:11)

H-Arg-Ile-Lys-Ile-Gly-Ile-Tyr-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (5) (SEQ ID NO:12)

H-Arg-Ile-Lys-Ile-Gly-Ile-Trp-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (6) (SEQ ID NO:13)

H-Arg-Ile-Lys-Leu-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (7) (SEQ ID NO:14)

H-Arg-Ile-Lys-Leu-Gly-Leu-Tyr-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (8) (SEQ ID NO:15)

H-Arg-Ile-Lys-Leu-Gly-Leu-Trp-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (9) (SEQ ID NO:16)

H-Arg-Ile-Lys-Leu-Gly-leu-Phe-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (10) (SEQ ID NO:17)

H-Arg-Ile-Lys-Leu-Gly-Ile-Tyr-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (11) (SEQ ID NO:18)

H-Arg-Ile-Lys-Leu-Gly-Ile-Trp-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (12) (SEQ ID NO:19)

H-Arg-Ile-Arg-Ile-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (13) (SEQ ID NO:20)

H-Arg-Ile-Arg-Ile-Gly-Leu-Tyr-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (14) (SEQ ID NO:21)

H-Arg-Ile-Arg-Ile-Gly-Leu-Trp-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (15) (SEQ ID NO:22)

H-Arg-Ile-Arg-Ile-Gly-Ile-Phe-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (16) (SEQ ID NO:23)

H-Arg-Ile-Arg-Ile-Gly-Ile-Tyr-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (17) (SEQ ID NO:24)

H-Arg-Ile-Arg-Ile-Gly-Ile-Trp-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (18) (SEQ ID NO:25)

H-Arg-Ile-Arg-Leu-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (19) (SEQ ID NO:26)

H-Arg-Ile-Arg-Leu-Gly-Leu-Tyr-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (20) (SEQ ID NO:27)

H-Arg-Ile-Arg-Leu-Gly-Leu-Trp-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (21) (SEQ ID NO:28)

H-Arg-Ile-Arg-Leu-Gly-Ile-Phe-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (22) (SEQ ID NO:29)

H-Arg-Ile-Arg-Leu-Gly-Ile-Tyr-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (23) (SEQ ID NO:30)

H-Arg-Ile-Arg-Leu-Gly-Ile-Trp-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (24) (SEQ ID NO:31)

H-Arg-Leu-Lys-Ile-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (25) (SEQ ID NO:32)

H-Arg-Leu-Lys-Ile-Gly-Leu-Tyr-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (26) (SEQ ID NO:33)

H-Arg-Leu-Lys-Ile-Gly-Leu-Trp-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (27) (SEQ ID NO:34)

H-Arg-Leu-Lys-Ile-Gly-Ile-Phe-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (28) (SEQ ID NO:35)

H-Arg-Leu-Lys-Ile-Gly-Ile-Tyr-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (29) (SEQ ID NO:36)

H-Arg-Leu-Lys-Ile-Gly-Ile-Trp-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (30) (SEQ ID NO:37)

H-Arg-Leu-Lys-Leu-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (31) (SEQ ID NO:38)

H-Arg-Leu-Lys-Leu-Gly-Leu-Tyr-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (32) (SEQ ID NO:39)

H-Arg-Leu-Lys-Leu-Gly-Leu-Trp-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (33) (SEQ ID NO:40)

H-Arg-Leu-Lys-Leu-Gly-Ile-Phe-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (34) (SEQ ID NO:41)

H-Arg-Leu-Lys-Leu-Gly-Ile-Tyr-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (35) (SEQ ID NO:42)

H-Arg-Leu-Lys-Leu-Gly-Ile-Trp-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (36) (SEQ ID NO:43)

H-Arg-Leu-Arg-Ile-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (37) (SEQ ID NO:44)

H-Arg-Leu-Arg-Ile-Gly-Leu-Tyr-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (38) (SEQ ID NO:45)

H-Arg-Leu-Arg-Ile-Gly-Leu-Trp-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (39) (SEQ ID NO:46)

H-Arg-Leu-Arg-Ile-Gly-Ile-Phe-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (40) (SEQ ID NO:47)

H-Arg-Leu-Arg-Ile-Gly-Ile-Tyr-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (41) (SEQ ID NO:48)

H-Arg-Leu-Arg-Ile-Gly-Ile-Trp-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (42) (SEQ ID NO:49)

H-Arg-Leu-Arg-Leu-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (43) (SEQ ID NO:50)

H-Arg-Leu-Arg-Leu-Gly-Leu-Tyr-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (44) (SEQ ID NO:51)

H-Arg-Leu-Arg-Leu-Gly-Leu-Trp-Asp-Gln-Leu-Ser-Lys-Leu-MH 2 (45) (SEQ ID NO:52)

H-Arg-Leu-Arg-Leu-Gly-Ile-Phe-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (46) (SEQ ID NO:53)

H-Arg-Leu-Arg-Leu-Gly-Ile-Tyr-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (47) (SEQ ID NO:54)

H-Arg-Leu-Arg-Leu-Gly-Ile-Trp-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (48) (SEQ ID NO:55)

H-Lys-Ile-Lys-Ile-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (49) (SEQ ID NO:56)

H-Lys-Ile-Lys-Ile-Gly-Leu-Tyr-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (50) (SEQ ID NO:57)

H-Lys-Ile-Lys-Ile-Gly-Leu-Trp-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (51) (SEQ ID NO:58)

H-Lys-Ile-Lys-Ile-Gly-Ile-Phe-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (52) (SEQ ID NO:59)

H-Lys-Ile-Lys-Ile-Gly-Ile-Tyr-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (53) (SEQ ID NO:60)

H-Lys-Ile-Lys-Ile-Gly-Ile-Trp-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (54) (SEQ ID NO:61)

H-Lys-Ile-Lys-Leu-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (55) (SEQ ID NO:62)

H-Lys-Ile-Lys-Leu-Gly-Leu-Tyr-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (56) (SEQ ID NO:63)

H-Lys-Ile-Lys-Leu-Gly-Leu-Trp-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (57) (SEQ ID NO:64)

H-Lys-Ile-Lys-Leu-Gly-Ile-Phe-Asp-Gln-Leu-Ser-Lys-Leu NH 2 (58) (SEQ ID NO:65)

H-Lys-Ile-Lys-Leu-Gly-Ile-Tyr-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (59) (SEQ ID NO:66)

H-Lys-Ile-Lys-Leu-Gly-Ile-Trp-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (60) (SEQ ID NO:67)

H-Lys-Ile-Arg-Ile-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (61) (SEQ ID NO:68)

H-Lys-Ile-Arg-Ile-Gly-Leu-Tyr-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (62) (SEQ ID NO:69)

H-Lys-Ile-Arg-Ile-Gly-Leu-Trp-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (63) (SEQ ID NO:70)

H-Lys-Ile-Arg-Ile-Gly-Ile-Phe-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (64) (SEQ ID NO:71)

H-Lys-Ile-Arg-Ile-Gly-Ile-Tyr-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (65) (SEQ ID NO:72)

H-Lys-Ile-Arg-Ile-Gly-Ile-Trp-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (66) (SEQ ID NO:73)

H-Lys-Ile-Arg-Leu-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (67) (SEQ ID NO:74)

H-Lys-Ile-Arg-Leu-Gly-Leu-Tyr-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (68) (SEQ ID NO:75)

H-Lys-Ile-Arg-Leu-Gly-Leu-Trp-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (69) (SEQ ID NO:76)

H-Lys-Ile-Arg-Leu-Gly-Ile-Phe-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (70) (SEQ ID NO:77)

H-Lys-Ile-Arg-Leu-Gly-Ile-Tyr-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (71) (SEQ ID NO:78)

H-Lys-Ile-Arg-Leu-Gly-Ile-Trp-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (72) (SEQ ID NO:79)

H-Lys-Leu-Lys-Ile-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (73) (SEQ ID NO:80)

H-Lys-Leu-Lys-Ile-Gly-Leu-Tyr-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (74) (SEQ ID NO:81)

H-Lys-Leu-Lys-Ile-Gly-Leu-Trp-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (75) (SEQ ID NO:82)

H-Lys-Leu-Lys-Ile-Gly-Ile-Phe-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (76) (SEQ ID NO:83)

H-Lys-Leu-Lys-Ile-Gly-Ile-Tyr-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (77) (SEQ ID NO:84)

H-Lys-Leu-Lys-Ile-Gly-Ile-Trp-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (78) (SEQ ID NO:85)

H-Lys-Leu-Lys-Leu-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (79) (SEQ ID NO:86)

H-Lys-Leu-Lys-Leu-Gly-Leu-Tyr-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (80) (SEQ ID NO:87)

H-Lys-Leu-Lys-Leu-Gly-Leu-Trp-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (81) (SEQ ID NO:88)

H-Lys-Leu-Lys-Leu-Gly-Ile-Phe-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (82) (SEQ ID NO:89)

H-Lys-Leu-Lys-Leu-Gly-Ile-Tyr-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (83) (SEQ ID NO:90)

H-Lys-Leu-Lys-Leu-Gly-Ile-Trp-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (84) (SEQ ID NO:91)

H-Lys-Leu-Arg-Ile-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (85) (SEQ ID NO:92)

H-Lys-Leu-Arg-Ile-Gly-Leu-Tyr-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (86) (SEQ ID NO:93)

H-Lys-Leu-Arg-Ile-Gly-Leu-Trp-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (87) (SEQ ID NO:94)

H-Lys-Leu-Arg-Ile-Gly-Ile-Phe-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (88) (SEQ ID NO:95)

H-Lys-Leu-Arg-Ile-Gly-Ile-Tyr-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (89) (SEQ ID NO:96)

H-Lys-Leu-Arg-Ile-Gly-Ile-Trp-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (90) (SEQ ID NO:97)

H-Lys-Leu-Arg-Leu-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (91) (SEQ ID NO:98)

H-Lys-Leu-Arg-Leu-Gly-Leu-Tyr-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (92) (SEQ ID NO:99)

H-Lys-Leu-Arg-Leu-Gly-Leu-Trp-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (93) (SEQ ID NO:100)

H-Lys-Leu-Arg-Leu-Gly-Ile-Phe-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (94) (SEQ ID NO:101)

H-Lys-Leu-Arg-Leu-Gly-Ile-Tyr-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (95) (SEQ ID NO:102)

H-Lys-Leu-Arg-Leu-Gly-Ile-Trp-Asp-Gln-Leu-Ser-Lys-Leu-NH 2 (96) (SEQ ID NO:103)

H-Arg-Ile-Lys-Ile-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (97) (SEQ ID NO:104)

H-Arg-Ile-Lys-Ile-Gly-Leu-Tyr-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (98) (SEQ ID NO:105)

H-Arg-Ile-Lys-Ile-Gly-Leu-Trp-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (99) (SEQ ID NO:106)

H-Arg-Ile-Lys-Ile-Gly-Ile-Phe-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (100) (SEQ ID NO:107)

H-Arg-Ile-Lys-Ile-Gly-Ile-Tyr-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (101) (SEQ ID NO:108)

H-Arg-Ile-Lys-Ile-Gly-Ile-Trp-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (102) (SEQ ID NO:109)

H-Arg-Ile-Lys-Leu-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (103) (SEQ ID NO:110)

H-Arg-Ile-Lys-Leu-Gly-Leu-Tyr-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (104) (SEQ ID NO:111)

H-Arg-Ile-Lys-Leu-Gly-Leu-Trp-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (105) (SEQ ID NO:112)

H-Arg-Ile-Lys-Leu-Gly-Ile-Phe-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (106) (SEQ ID NO:113)

H-Arg-Ile-Lys-Leu-Gly-Ile-Tyr-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (107) (SEQ ID NO:114)

H-Arg-Ile-Lys-Leu-Gly-Ile-Trp-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (108) (SEQ ID NO:115)

H-Arg-Ile-Arg-Ile-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (109) (SEQ ID NO:116)

H-Arg-Ile-Arg-Ile-Gly-Leu-Tyr-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (110) (SEQ ID NO:117)

H-Arg-Ile-Arg-Ile-Gly-Leu-Trp-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (111) (SEQ ID NO:118)

H-Arg-Ile-Arg-Ile-Gly-Ile-Phe-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (112) (SEQ ID NO:119)

H-Arg-Ile-Arg-Ile-Gly-Ile-Tyr-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (113) (SEQ ID NO:120)

H-Arg-Ile-Arg-Ile-Gly-Ile-Trp-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (114) (SEQ ID NO:121)

H-Arg-Ile-Arg-Leu-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (115) (SEQ ID NO:122)

H-Arg-Ile-Arg-Leu-Gly-Leu-Tyr-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (116) (SEQ ID NO:123)

H-Arg-Ile-Arg-Leu-Gly-Leu-Trp-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (117) (SEQ ID NO:124)

H-Arg-Ile-Arg-Leu-Gly-Ile-Phe-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (118) (SEQ ID NO:125)

H-Arg-Ile-Arg-Leu-Gly-Ile-Tyr-Asp-Gln-Leu-Ser-Arg-Let-NH 2 (119) (SEQ ID NO:126)

H-Arg-Ile-Arg-Leu-Gly-Ile-Trp-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (120) (SEQ ID NO:127)

H-Arg-Leu-Lys-Ile-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (121) (SEQ ID NO:128)

H-Arg-Leu-Lys-Ile-Gly-Leu-Tyr-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (122) (SEQ ID NO:129)

H-Arg-Leu-Lys-Ile-Gly-Leu-Trp-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (123) (SEQ ID NO:130)

H-Arg-Leu-Lys-Ile-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (124) (SEQ ID NO:131)

H-Arg-Leu-Lys-Ile-Gly-Ile-Tyr-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (125) (SEQ ID NO:132)

H-Arg-Leu-Lys-Ile-Gly-Ile-Trp-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (126) (SEQ ID NO:133)

H-Arg-Leu-Lys-Ile-Gly-Ile-Phe-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (127) (SEQ ID NO:134)

H-Arg-Leu-Lys-Leu-Gly-Leu-Tyr-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (128) (SEQ ID NO:135)

H-Arg-Leu-Lys-Leu-Gly-Leu-Trp-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (129) (SEQ ID NO:136)

H-Arg-Leu-Lys-Leu-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (130) (SEQ ID NO:137)

H-Arg-Leu-Lys-Leu-Gly-Ile-Tyr-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (131) (SEQ ID NO:138)

H-Arg-Leu-Lys-Leu-Gly-Ile-Trp-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (132) (SEQ ID NO:139)

H-Arg-Leu-Lys-Leu-Gly-LIe-Phe-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (133) (SEQ ID NO:140)

H-Arg-Leu-Arg-Ile-Gly-Leu-Tyr-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (134) (SEQ ID NO:141)

H-Arg-Leu-Arg-Ile-Gly-Leu-Trp-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (135) (SEQ ID NO:142)

H-Arg-Leu-Arg-Ile-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (136) (SEQ ID NO:143)

H-Arg-Leu-Arg-Ile-Gly-Ile-Tyr-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (137) (SEQ ID NO:144)

H-Arg-Leu-Arg-Ile-Gly-Ile-Trp-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (138) (SEQ ID NO:145)

H-Arg-Leu-Arg-Ile-Gly-Ile-Phe-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (139) (SEQ ID NO:146)

H-Arg-Leu-Arg-Leu-Gly-Leu-Tyr-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (140) (SEQ ID NO:147)

H-Arg-Leu-Arg-Leu-Gly-Leu-Trp-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (141) (SEQ ID NO:148)

H-Arg-Leu-Arg-Leu-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (142) (SEQ ID NO:149)

H-Arg-Leu-Arg-Leu-Gly-Ile-Tyr-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (143) (SEQ ID NO:150)

H-Arg-Leu-Arg-Leu-Gly-Ile-Trp-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (144) (SEQ ID NO:151)

H-Lys-Ile-Lys-Ile-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (145) (SEQ ID NO:152)

H-Lys-Ile-Lys-Ile-Gly-Leu-Tyr-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (146) (SEQ ID NO:153)

H-Lys-Ile-Lys-Ile-Gly-Leu-Trp-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (147) (SEQ ID NO:154)

H-Lys-Ile-Lys-Ile-Gly-Ile-Phe-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (148) (SEQ ID NO:155)

H-Lys-Ile-Lys-Ile-Gly-Ile-Tyr-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (149) (SEQ ID NO:156)

H-Lys-Ile-Lys-Ile-Gly-Ile-Trp-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (150) (SEQ ID NO:157)

H-Lys-Ile-Lys-Leu-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (151) (SEQ ID NO:158)

H-Lys-Ile-Lys-Leu-Gly-Leu-Tyr-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (152) (SEQ ID NO:159)

H-Lys-Ile-Lys-Leu-Gly-Leu-Trp-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (153) (SEQ ID NO:160)

H-Lys-Ile-Lys-Leu-Gly-Ile-Phe-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (154) (SEQ ID NO:161)

H-Lys-Ile-Lys-Leu-Gly-Ile-Tyr-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (155) (SEQ ID NO:162)

H-Lys-Ile-Lys-Leu-Gly-Ile-Trp-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (156) (SEQ ID NO:163)

H-Lys-Ile-Arg-Ile-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (157) (SEQ ID NO:164)

H-Lys-Ile-Arg-Ile-Gly-Leu-Tyr-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (158) (SEQ ID NO:165)

H-Lys-Ile-Arg-Ile-Gly-Leu-Trp-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (159) (SEQ ID NO:166)

H-Lys-Ile-Arg-Ile-Gly-ILe-Phe-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (160) (SEQ ID NO:167)

H-Lys-Ile-Arg-Ile-Gly-Ile-Tyr-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (161) (SEQ ID NO:168)

H-Lys-Ile-Arg-Ile-Gly-Ile-Trp-Asp-Gln-Leu-Ser-Arg-Leu NH 2 (162) (SEQ ID NO:169)

H-Lys-Ile-Arg-Leu-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (163) (SEQ ID NO:170)

H-Lys-Ile-Arg-Leu-Gly-Leu-Tyr-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (164) (SEQ ID NO:171)

H-Lys-Ile-Arg-Leu-Gly-Leu-Trp-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (165) (SEQ ID NO:172)

H-Lys-Ile-Arg-Leu-Gly-Ile-Phe-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (166) (SEQ ID NO:173)

H-Lys-Ile-Arg-Leu-Gly-LIe-Tyr-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (167) (SEQ ID NO:174)

H-Lys-Ile-Arg-Leu-Gly-Ile-Trp-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (168) (SEQ ID NO:175)

H-Lys-Leu-Lys-ILe-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (169) (SEQ ID NO:176)

H-Lys-Leu-Lys-Ile-Gly-Leu-Tyr-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (170) (SEQ ID NO:177)

H-Lys-Leu-Lys-Ile-Gly-Leu-Trp-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (171) (SEQ ID NO:178)

H-Lys-Leu-Lys-Ile-Gly-Ile-Phe-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (172) (SEQ ID NO:179)

H-Lys-Leu-Lys-Ile-Gly-Leu-Tyr-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (173) (SEQ ID NO:180)

H-Lys-Leu-Lys-Ile-Gly-Ile-Trp-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (174) (SEQ ID NO:181)

H-Lys-Leu-Lys-Leu-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (175) (SEQ ID NO:182)

H-Lys-Leu-Lys-Leu-Gly-Leu-Tyr-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (176) (SEQ ID NO:183)

H-Lys-Leu-Lys-Leu-Gly-Leu-Trp-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (177) (SEQ ID NO:184)

H-Lys-Leu-Lys-Leu-Gly-Ile-Phe-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (178) (SEQ ID NO:185)

H-Lys-Leu-Lys-Leu-Gly-Ile-Tyr-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (179) (SEQ ID NO:186)

H-Lys-Leu-Lys-Leu-Gly-Ile-Trp-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (180) (SEQ ID NO:187)

H-Lys-Leu-Arg-Ile-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (181) (SEQ ID NO:188)

H-Lys-Leu-Arg-Ile-Gly-Leu-Tyr-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (182) (SEQ ID NO:189)

H-Lys-Leu-Arg-Ile-Gly-Leu-Trp-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (183) (SEQ ID NO:190)

H-Lys-Leu-Arg-Ile-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (184) (SEQ ID NO:191)

H-Lys-Leu-Arg-Ile-Gly-Ile-Tyr-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (185) (SEQ ID NO:192)

H-Lys-Leu-Arg-ILe-Gly-Leu-Trp-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (186) (SEQ ID NO:193)

H-Lys-Leu-Arg-Ile-Gly-Ile-Phe-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (187) (SEQ ID NO:194)

H-Lys-Leu-Arg-Leu-Gly-Leu-Tyr-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (188) (SEQ ID NO:195)

H-Lys-Leu-Arg-Leu-Gly-Leu-Trp-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (189) (SEQ ID NO:196)

H-Lys-Leu-Arg-Leu-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (190) (SEQ ID NO:197)

H-Lys-Leu-Arg-Leu-Gly-Ile-Tyr-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (191) (SEQ ID NO:198)

H-Lys-Leu-Arg-Leu-Gly-Ile-Trp-Asp-Gln-Leu-Ser-Arg-Leu-NH 2 (192) (SEQ ID NO:199)

In order to obtain the peptides of the present invention, for example, venom sac of a solitary wasp containing said peptides may be excised and then homogenized in a water-containing organic solvent, and the resulting homogenate may be centrifuged to obtain a supernatant, which may be purified by a reversed phase chromatography until finally it exhibits a single peak when monitored by UV absorbance at 215 nm, thereby isolating and purifying the desired compound.

The water-containing organic solvent to be used for the homogenization during the above purification process means a mixture of water and an organic solvent that is freely miscible with water, and may be any solvent which permits extraction of the compound of the present invention. Examples include, but not limited to, water-containing acetone, water-containing acetonitrile, and the like. When the resulting supernatant is directly applied to the reversed phase chromatography, it is preferred that about 0.1% of trifluoroacetic acid (hereinafter referred to as TFA) is added to such a water-containing organic solvent.

Since the peptides provided by the present invention consist of at most about 13 amino acids, they can be synthesized by the conventional liquid or solid phase method. Furthermore, since the peptides of the present invention are basic peptides, they can be converted to appropriate acid-added salts according to conventional technique. Such preferred acid-added salts may be obtained by reaction with a pharmaceutically acceptable acid, and said salts include, for example, lactates, acetates, succinates, maleates, fumarates, tartarates, citrates, gluconates, ascorbates, benzoates, methanesulfonates, cinnamates, benzenesulfonates or phosphates, hydrogenphosphates, hydrochlorides, hydrobromides, hydroiodides, sulfamates, sulfates, trifluoroacetates, and the like.

The biological activity of the present peptides can be assayed according to the methods described in Japanese Patent Laid-Open No. 4-198161, in which excitatory postsynaptic potential (EPSP) is generated in the neuromuscular specimen of a lobster's walking leg, and the effect of the compound given to the nerve fibers on the EPSP is determined.

In general, substances inhibiting EPSP are believed to be glutamate antagonists or inhibitors for the release of glutamic acid, and the substances enhancing EPSP are believed to be glutamate-like agonists or accelerators for the release of glutamic acid.

As described in the Examples below, the peptides of the present invention show a remarkable effect of enhancing EPSP determined by the above assay. Accordingly, the compounds of the present invention are useful for enhancing cerebral neural activities and recovering muscular strength in the treatment of neuromuscular diseases. They are also useful as a tool for the study of neuroscience toward the elucidation of the transmission mechanism.

The present invention is now illustrated in more detail by way of the following examples, but it is to be noted that the present invention is not limited by these Examples in any way.

EXAMPLE 1

Isolation and Structure Determination of Peptides (1) and (97)

1) Isolation of Peptide (1)

The venom sacs of 60 female Anoplius samariensis were excised and lyophilized. These were homogenized in 1 ml of 50% acetonitrile/water containing 0.1% TFA and then centrifuged to obtain an extract. The precipitate was centrifuged again with 1 ml of 50% acetonitrile/water containing 0.1% TFA. This procedure was then repeated four times. All the extracts resulting from the above procedure carried out five times in total were collected and then evaporated under reduced pressure to obtain a crude extract.

The resulting crude extract was dissolved in water and then subjected to reversed phase HPLC (Waters Associates) using CAPCELL PAK C 18 φ 10 mm×250 mm (Shiseido Co., Ltd.,) with linear gradient from 5% to 95% acetonitrile/water containing 0.1% TFA at a flow rate of 2.5 ml/min over 30 minutes at room temperature. The peak fraction at a retention time of 19 min was collected by monitoring UV absorbance at 215 nm.

The obtained peak fraction was further subjected to HPLC using CAPCELL PAK C 18 φ 6 mm×150 mm (Shiseido Co., Ltd.,) with isocratic 29% acetonitrile/water containing 0.1% TFA at a flow rate of 1 ml/min at room temperature, and the peak fraction at a retention time of 15 min was collected by monitoring UV absorbance at 215 nm. This fraction showed a single peak at a retention time of 11 min in HPLC using the above column (isocratic 30% acetonitrile/water containing 0.1% TFA).

The resulting fraction was lyophilized to yield 0.1 mg of peptide (1) as a trifluoroacetate.

2) Isolation of Peptide (97)

The venom sacs of 29 female Batozonellus maculifrons were excised and lyophilized. These were homogenized in 0.5 ml of 50% acetonitrile/water containing 0.1% TFA and then centrifuged to obtain an extract. The precipitate was centrifuged again with 0.5 ml of 50% acetonitrile/water containing 0.1% TFA. This procedure was then repeated four times. All the extracts resulting from the above procedure carried out five times in total were collected and then evaporated under reduced pressure to obtain a crude extract.

The resulting crude extract was dissolved in water and then subjected to reversed phase HPLC using CAPCELL PAK C 18 φ 10 mm×250 mm with linear gradient from 5% to 95% acetonitrile/water containing 0.1% TFA at a flow rate of 2.5 ml/min over 30 minutes at room temperature. The peak fraction at a retention time of 19 min was collected by monitoring UV absorbance at 215 nm.

The obtained peak fraction was further subjected to HPLC using CAPCELL PAK C 18 φ 6 mm×150 mm with isocratic 29% acetonitrile/water containing 0.1% TFA at a flow rate of 1 ml/min at room temperature, and the peak fractions at a retention time of 15 min and 16 min were collected by monitoring UV absorbance at 215 nm. The fraction obtained at a retention time of 15 min was lyophilized to yield 50 μg of peptide (1) as a trifluoroacetate and the fraction obtained at a retention time of 16 min was lyophilized to yield 30 μg of peptide (97) as atrifluoroacetate.

3) Determination of the Amino Acid Sequence

The amino acid sequences of the resulting peptides were determined by mass spectroscopy and Edman degradation. Mass spectroscopy was conducted by the Ladder sequencing method using carboxypeptidase and aminopeptidase and by MALDI-TOF-MS combined with the CID method. Distinction of Leu from Ile and Lys from Gln was demonstrated by the automatic Edman degradation using ABI 477A/120A Protein Sequencer (Applied Biosystems).

Furthermore, since a peak of m/z=1530 (M+H) + was observed in MALDI-TOF-MS, peptide (1) was found to have a sequence represented by SEQ ID NO: 1 in which the N-terminal is free and the C-terminal is amidated.

On the other hand, peptide (97) was identified with a sequence represented by SEQ ID NO: 2 by observing a peak of m/z=1558 (M+H) + in MALDI-TOF-MS.

EXAMPLE 2

Synthesis of Peptides (1) and (97)

Peptides (1) and (97) were synthesized using TGS-RAM-Resin (Shimadzu Corporation) as a carrier and Fmoc-amino acids in the solid phase method using the automatic peptide synthesizer PSSM-8 (Shimadzu Corporation).

Each of the synthesized peptides was then cleaved from the peptide resin and deprotected by adding a TFA solution containing 5% phenol, 5% thioanisole, 5% water, 3% 1,2-ethanedithiol and 2% ethylmethyl disulfide in an amount of 10 ml per gram of the peptide resin and then treating it at room temperature for 8 hours. After the treatment, ether was added to the TFA solution to precipitate the peptides, and the precipitate was washed three times with ether to obtain crude peptides. The crude peptides were purified by C-18 reversed phase HPLC. The resulting synthetic peptides (1) and (97) showed the same retention time in HPLC, the same mass spectra, and the same biological activity as the natural peptides (1) and (97), respectively.

EXAMPLE 3

Measurement of the Effect on Excitatory Postsynaptic Potential (EPSP)

The effect of the present peptides on excitatory postsynaptic potential (EPSP) was measured according to the method disclosed in Japanese Patent Laid-Open No. 4-198161. Thus, the shell of a lobster's walking leg was removed to expose the excitatory nerve and the inhibitory nerve, and a stimulating electrode was attached thereto. Then the nerve-muscle junction was exposed, and a recording electrode was attached thereto. The walking leg equipped with the electrodes was transferred to a container filled with an artificial seawater, and a partition was set up between the stimulating electrode part and the recording electrode part. The samples to be measured were dissolved into the artificial seawater in the recording electrode side (i.e., the side containing the nerve-muscle junction). Subsequently, the excitatory nerve was electrically stimulated and the EPSP, which was induced by glutamic acid released from the nerve end in response to the stimulation, was recorded.

When the effects of peptides (1) and (97) on EPSP were studied according to this method, peptide (1) enhanced EPSP at a concentration of 1×10 −6 M, and peptide (97) did at 2×10 −7 M.

INDUSTRIAL APPLICABILITY

The peptides provided by the present invention can be used as useful reagents to study the structure-activity relationship of their activities on the glutamate receptor in the field of neuroscience. Furthermore, they can be used as standard compounds in the study of neuroscience, especially in the study of neuropathic diseases such as Huntington's disease, epilepsy, Parkinson's disease and senile dementia, paving the way for pharmaceutical application of substances that act on the glutamate receptor.

203 1 13 PRT Anoplius samariensis 1Arg Ile Lys Ile Gly Leu Phe Asp Gln Leu Ser Lys Leu1 5 10 2 13 PRT Batozonellus maculifrons 2Arg Ile Lys Ile Gly Leu Phe Asp Gln Leu Ser Arg Leu1 5 10 3 4 PRT Pompilid sp. 3Leu Ser Lys Leu1 4 4 PRT Pompilid sp. 4Leu Ser Arg Leu1 5 12 PRT Pompilid sp. MISC_FEATURE (1)..(1) Arg or Lys 5Xaa Xaa Xaa Xaa Gly Xaa Xaa Asp Gln Leu Ser Lys1 5 10 6 12 PRT Pompilid sp. MISC_FEATURE (1)..(1) Arg or Lys 6Xaa Xaa Xaa Xaa Gly Xaa Xaa Asp Gln Leu Ser Arg1 5 10 7 13 PRT Pompilid sp. MISC_FEATURE (1)..(1) Arg or Lys 7Xaa Xaa Xaa Xaa Gly Xaa Xaa Asp Gln Leu Ser Lys Leu1 5 10 8 13 PRT Pompilid sp. MISC_FEATURE (1)..(1) Arg or Lys 8Xaa Xaa Xaa Xaa Gly Xaa Xaa Asp Gln Leu Ser Arg Leu1 5 10 9 13 PRT Pompilid sp. 9Arg Ile Lys Ile Gly Leu Tyr Asp Gln Leu Ser Lys Leu1 5 10 10 13 PRT Pompilid sp. 10Arg Ile Lys Ile Gly Leu Trp Asp Gln Leu Ser Lys Leu1 5 10 11 13 PRT Pompilid sp. 11Arg Ile Lys Ile Gly Ile Phe Asp Gln Leu Ser Lys Leu1 5 10 12 13 PRT Pompilid sp. 12Arg Ile Lys Ile Gly Ile Tyr Asp Gln Leu Ser Lys Leu1 5 10 13 13 PRT Pompilid sp. 13Arg Ile Lys Ile Gly Ile Trp Asp Gln Leu Ser Lys Leu1 5 10 14 13 PRT Pompilid sp. 14Arg Ile Lys Leu Gly Leu Phe Asp Gln Leu Ser Lys Leu1 5 10 15 13 PRT Pompilid sp. 15Arg Ile Lys Leu Gly Leu Tyr Asp Gln Leu Ser Lys Leu1 5 10 16 13 PRT Pompilid sp. 16Arg Ile Lys Leu Gly Leu Trp Asp Gln Leu Ser Lys Leu1 5 10 17 13 PRT Pompilid sp. 17Arg Ile Lys Leu Gly Ile Phe Asp Gln Leu Ser Lys Leu1 5 10 18 13 PRT Pompilid sp. 18Arg Ile Lys Leu Gly Ile Tyr Asp Gln Leu Ser Lys Leu1 5 10 19 13 PRT Pompilid sp. 19Arg Ile Lys Leu Gly Ile Trp Asp Gln Leu Ser Lys Leu1 5 10 20 13 PRT Pompilid sp. 20Arg Ile Arg Ile Gly Leu Phe Asp Gln Leu Ser Lys Leu1 5 10 21 13 PRT Pompilid sp. 21Arg Ile Arg Ile Gly Leu Tyr Asp Gln Leu Ser Lys Leu1 5 10 22 13 PRT Pompilid sp. 22Arg Ile Arg Ile Gly Leu Trp Asp Gln Leu Ser Lys Leu1 5 10 23 13 PRT Pompilid sp. 23Arg Ile Arg Ile Gly Ile Phe Asp Gln Leu Ser Lys Leu1 5 10 24 13 PRT Pompilid sp. 24Arg Ile Arg Ile Gly Ile Tyr Asp Gln Leu Ser Lys Leu1 5 10 25 13 PRT Pompilid sp. 25Arg Ile Arg Ile Gly Ile Trp Asp Gln Leu Ser Lys Leu1 5 10 26 13 PRT Pompilid sp. 26Arg Ile Arg Leu Gly Leu Phe Asp Gln Leu Ser Lys Leu1 5 10 27 13 PRT Pompilid sp. 27Arg Ile Arg Leu Gly Leu Tyr Asp Gln Leu Ser Lys Leu1 5 10 28 13 PRT Pompilid sp. 28Arg Ile Arg Leu Gly Leu Trp Asp Gln Leu Ser Lys Leu1 5 10 29 13 PRT Pompilid sp. 29Arg Ile Arg Leu Gly Ile Phe Asp Gln Leu Ser Lys Leu1 5 10 30 13 PRT Pompilid sp. 30Arg Ile Arg Leu Gly Ile Tyr Asp Gln Leu Ser Lys Leu1 5 10 31 13 PRT Pompilid sp. 31Arg Ile Arg Leu Gly Ile Trp Asp Gln Leu Ser Lys Leu1 5 10 32 13 PRT Pompilid sp. 32Arg Leu Lys Ile Gly Leu Phe Asp Gln Leu Ser Lys Leu1 5 10 33 13 PRT Pompilid sp. 33Arg Leu Lys Ile Gly Leu Tyr Asp Gln Leu Ser Lys Leu1 5 10 34 13 PRT Pompilid sp. 34Arg Leu Lys Ile Gly Leu Trp Asp Gln Leu Ser Lys Leu1 5 10 35 13 PRT Pompilid sp. 35Arg Leu Lys Ile Gly Ile Phe Asp Gln Leu Ser Lys Leu1 5 10 36 13 PRT Pompilid sp. 36Arg Leu Lys Ile Gly Ile Tyr Asp Gln Leu Ser Lys Leu1 5 10 37 13 PRT Pompilid sp. 37Arg Leu Lys Ile Gly Ile Trp Asp Gln Leu Ser Lys Leu1 5 10 38 13 PRT Pompilid sp. 38Arg Leu Lys Leu Gly Leu Phe Asp Gln Leu Ser Lys Leu1 5 10 39 13 PRT Pompilid sp. 39Arg Leu Lys Leu Gly Leu Tyr Asp Gln Leu Ser Lys Leu1 5 10 40 13 PRT Pompilid sp. 40Arg Leu Lys Leu Gly Leu Trp Asp Gln Leu Ser Lys Leu1 5 10 41 13 PRT Pompilid sp. 41Arg Leu Lys Leu Gly Ile Phe Asp Gln Leu Ser Lys Leu1 5 10 42 13 PRT Pompilid sp. 42Arg Leu Lys Leu Gly Ile Tyr Asp Gln Leu Ser Lys Leu1 5 10 43 13 PRT Pompilid sp. 43Arg Leu Lys Leu Gly Ile Trp Asp Gln Leu Ser Lys Leu1 5 10 44 13 PRT Pompilid sp. 44Arg Leu Arg Ile Gly Leu Phe Asp Gln Leu Ser Lys Leu1 5 10 45 13 PRT Pompilid sp. 45Arg Leu Arg Ile Gly Leu Tyr Asp Gln Leu Ser Lys Leu1 5 10 46 13 PRT Pompilid sp. 46Arg Leu Arg Ile Gly Leu Trp Asp Gln Leu Ser Lys Leu1 5 10 47 13 PRT Pompilid sp. 47Arg Leu Arg Ile Gly Ile Phe Asp Gln Leu Ser Lys Leu1 5 10 48 13 PRT Pompilid sp. 48Arg Leu Arg Ile Gly Ile Tyr Asp Gln Leu Ser Lys Leu1 5 10 49 13 PRT Pompilid sp. 49Arg Leu Arg Ile Gly Ile Trp Asp Gln Leu Ser Lys Leu1 5 10 50 13 PRT Pompilid sp. 50Arg Leu Arg Leu Gly Leu Phe Asp Gln Leu Ser Lys Leu1 5 10 51 13 PRT Pompilid sp. 51Arg Leu Arg Leu Gly Leu Tyr Asp Gln Leu Ser Lys Leu1 5 10 52 13 PRT Pompilid sp. 52Arg Leu Arg Leu Gly Leu Trp Asp Gln Leu Ser Lys Leu1 5 10 53 13 PRT Pompilid sp. 53Arg Leu Arg Leu Gly Ile Phe Asp Gln Leu Ser Lys Leu1 5 10 54 13 PRT Pompilid sp. 54Arg Leu Arg Leu Gly Ile Tyr Asp Gln Leu Ser Lys Leu1 5 10 55 13 PRT Pompilid sp. 55Arg Leu Arg Leu Gly Ile Trp Asp Gln Leu Ser Lys Leu1 5 10 56 13 PRT Pompilid sp. 56Lys Ile Lys Ile Gly Leu Phe Asp Gln Leu Ser Lys Leu1 5 10 57 13 PRT Pompilid sp. 57Lys Ile Lys Ile Gly Leu Tyr Asp Gln Leu Ser Lys Leu1 5 10 58 13 PRT Pompilid sp. 58Lys Ile Lys Ile Gly Leu Trp Asp Gln Leu Ser Lys Leu1 5 10 59 13 PRT Pompilid sp. 59Lys Ile Lys Ile Gly Ile Phe Asp Gln Leu Ser Lys Leu1 5 10 60 13 PRT Pompilid sp. 60Lys Ile Lys Ile Gly Ile Tyr Asp Gln Leu Ser Lys Leu1 5 10 61 13 PRT Pompilid sp. 61Lys Ile Lys Ile Gly Ile Trp Asp Gln Leu Ser Lys Leu1 5 10 62 13 PRT Pompilid sp. 62Lys Ile Lys Leu Gly Leu Phe Asp Gln Leu Ser Lys Leu1 5 10 63 13 PRT Pompilid sp. 63Lys Ile Lys Leu Gly Leu Tyr Asp Gln Leu Ser Lys Leu1 5 10 64 13 PRT Pompilid sp. 64Lys Ile Lys Leu Gly Leu Trp Asp Gln Leu Ser Lys Leu1 5 10 65 13 PRT Pompilid sp. 65Lys Ile Lys Leu Gly Ile Phe Asp Gln Leu Ser Lys Leu1 5 10 66 13 PRT Pompilid sp. 66Lys Ile Lys Leu Gly Ile Tyr Asp Gln Leu Ser Lys Leu1 5 10 67 13 PRT Pompilid sp. 67Lys Ile Lys Leu Gly Ile Trp Asp Gln Leu Ser Lys Leu1 5 10 68 13 PRT Pompilid sp. 68Lys Ile Arg Ile Gly Leu Phe Asp Gln Leu Ser Lys Leu1 5 10 69 13 PRT Pompilid sp. 69Lys Ile Arg Ile Gly Leu Tyr Asp Gln Leu Ser Lys Leu1 5 10 70 13 PRT Pompilid sp. 70Lys Ile Arg Ile Gly Leu Trp Asp Gln Leu Ser Lys Leu1 5 10 71 13 PRT Pompilid sp. 71Lys Ile Arg Ile Gly Ile Phe Asp Gln Leu Ser Lys Leu1 5 10 72 13 PRT Pompilid sp. 72Lys Ile Arg Ile Gly Ile Tyr Asp Gln Leu Ser Lys Leu1 5 10 73 13 PRT Pompilid sp. 73Lys Ile Arg Ile Gly Ile Trp Asp Gln Leu Ser Lys Leu1 5 10 74 13 PRT Pompilid sp. 74Lys Ile Arg Leu Gly Leu Phe Asp Gln Leu Ser Lys Leu1 5 10 75 12 PRT Pompilid sp. 75Lys Ile Arg Leu Gly Tyr Asp Gln Leu Ser Lys Leu1 5 10 76 13 PRT Pompilid sp. 76Lys Ile Arg Leu Gly Leu Trp Asp Gln Leu Ser Lys Leu1 5 10 77 13 PRT Pompilid sp. 77Lys Ile Arg Leu Gly Ile Phe Asp Gln Leu Ser Lys Leu1 5 10 78 13 PRT Pompilid sp. 78Lys Ile Arg Leu Gly Ile Tyr Asp Gln Leu Ser Lys Leu1 5 10 79 13 PRT Pompilid sp. 79Lys Ile Arg Leu Gly Ile Trp Asp Gln Leu Ser Lys Leu1 5 10 80 13 PRT Pompilid sp. 80Lys Leu Lys Ile Gly Leu Phe Asp Gln Leu Ser Lys Leu1 5 10 81 13 PRT Pompilid sp. 81Lys Leu Lys Ile Gly Leu Tyr Asp Gln Leu Ser Lys Leu1 5 10 82 13 PRT Pompilid sp. 82Lys Leu Lys Ile Gly Leu Trp Asp Gln Leu Ser Lys Leu1 5 10 83 13 PRT Pompilid sp. 83Lys Leu Lys Ile Gly Ile Phe Asp Gln Leu Ser Lys Leu1 5 10 84 13 PRT Pompilid sp. 84Lys Leu Lys Ile Gly Ile Tyr Asp Gln Leu Ser Lys Leu1 5 10 85 13 PRT Pompilid sp. 85Lys Leu Lys Ile Gly Ile Trp Asp Gln Leu Ser Lys Leu1 5 10 86 13 PRT Pompilid sp. 86Lys Leu Lys Leu Gly Leu Phe Asp Gln Leu Ser Lys Leu1 5 10 87 13 PRT Pompilid sp. 87Lys Leu Lys Leu Gly Leu Tyr Asp Gln Leu Ser Lys Leu1 5 10 88 13 PRT Pompilid sp. 88Lys Leu Lys Leu Gly Leu Trp Asp Gln Leu Ser Lys Leu1 5 10 89 13 PRT Pompilid sp. 89Lys Leu Lys Leu Gly Ile Phe Asp Gln Leu Ser Lys Leu1 5 10 90 13 PRT Pompilid sp. 90Lys Leu Lys Leu Gly Ile Tyr Asp Gln Leu Ser Lys Leu1 5 10 91 13 PRT Pompilid sp. 91Lys Leu Lys Leu Gly Ile Trp Asp Gln Leu Ser Lys Leu1 5 10 92 13 PRT Pompilid sp. 92Lys Leu Arg Ile Gly Leu Phe Asp Gln Leu Ser Lys Leu1 5 10 93 13 PRT Pompilid sp. 93Lys Leu Arg Ile Gly Leu Tyr Asp Gln Leu Ser Lys Leu1 5 10 94 13 PRT Pompilid sp. 94Lys Leu Arg Ile Gly Leu Trp Asp Gln Leu Ser Lys Leu1 5 10 95 13 PRT Pompilid sp. 95Lys Leu Arg Ile Gly Ile Phe Asp Gln Leu Ser Lys Leu1 5 10 96 13 PRT Pompilid sp. 96Lys Leu Arg Ile Gly Ile Tyr Asp Gln Leu Ser Lys Leu1 5 10 97 13 PRT Pompilid sp. 97Lys Leu Arg Ile Gly Ile Trp Asp Gln Leu Ser Lys Leu1 5 10 98 13 PRT Pompilid sp. 98Lys Leu Arg Leu Gly Leu Phe Asp Gln Leu Ser Lys Leu1 5 10 99 13 PRT Pompilid sp. 99Lys Leu Arg Leu Gly Leu Tyr Asp Gln Leu Ser Lys Leu1 5 10 100 13 PRT Pompilid sp. 100Lys Leu Arg Leu Gly Leu Trp Asp Gln Leu Ser Lys Leu1 5 10 101 13 PRT Pompilid sp. 101Lys Leu Arg Leu Gly Ile Phe Asp Gln Leu Ser Lys Leu1 5 10 102 13 PRT Pompilid sp. 102Lys Leu Arg Leu Gly Ile Tyr Asp Gln Leu Ser Lys Leu1 5 10 103 13 PRT Pompilid sp. 103Lys Leu Arg Leu Gly Ile Trp Asp Gln Leu Ser Lys Leu1 5 10 104 13 PRT Pompilid sp. 104Arg Ile Lys Ile Gly Leu Tyr Asp Gln Leu Ser Arg Leu1 5 10 105 13 PRT Pompilid sp. 105Arg Ile Lys Ile Gly Leu Trp Asp Gln Leu Ser Arg Leu1 5 10 106 13 PRT Pompilid sp. 106Arg Ile Lys Ile Gly Ile Phe Asp Gln Leu Ser Arg Leu1 5 10 107 13 PRT Pompilid sp. 107Arg Ile Lys Ile Gly Ile Tyr Asp Gln Leu Ser Arg Leu1 5 10 108 13 PRT Pompilid sp. 108Arg Ile Lys Ile Gly Ile Trp Asp Gln Leu Ser Arg Leu1 5 10 109 13 PRT Pompilid sp. 109Arg Ile Lys Leu Gly Leu Phe Asp Gln Leu Ser Arg Leu1 5 10 110 13 PRT Pompilid sp. 110Arg Ile Lys Leu Gly Leu Tyr Asp Gln Leu Ser Arg Leu1 5 10 111 13 PRT Pompilid sp. 111Arg Ile Lys Leu Gly Leu Trp Asp Gln Leu Ser Arg Leu1 5 10 112 13 PRT Pompilid sp. 112Arg Ile Lys Leu Gly Ile Phe Asp Gln Leu Ser Arg Leu1 5 10 113 13 PRT Pompilid sp. 113Arg Ile Lys Leu Gly Ile Tyr Asp Gln Leu Ser Arg Leu1 5 10 114 13 PRT Pompilid sp. 114Arg Ile Lys Leu Gly Ile Trp Asp Gln Leu Ser Arg Leu1 5 10 115 13 PRT Pompilid sp. 115Arg Ile Arg Ile Gly Leu Phe Asp Gln Leu Ser Arg Leu1 5 10 116 13 PRT Pompilid sp. 116Arg Ile Arg Ile Gly Leu Tyr Asp Gln Leu Ser Arg Leu1 5 10 117 13 PRT Pompilid sp. 117Arg Ile Arg Ile Gly Leu Trp Asp Gln Leu Ser Arg Leu1 5 10 118 13 PRT Pompilid sp. 118Arg Ile Arg Ile Gly Ile Phe Asp Gln Leu Ser Arg Leu1 5 10 119 13 PRT Pompilid sp. 119Arg Ile Arg Ile Gly Ile Tyr Asp Gln Leu Ser Arg Leu1 5 10 120 13 PRT Pompilid sp. 120Arg Ile Arg Ile Gly Ile Trp Asp Gln Leu Ser Arg Leu1 5 10 121 13 PRT Pompilid sp. 121Arg Ile Arg Leu Gly Leu Phe Asp Gln Leu Ser Arg Leu1 5 10 122 13 PRT Pompilid sp. 122Arg Ile Arg Leu Gly Leu Tyr Asp Gln Leu Ser Arg Leu1 5 10 123 13 PRT Pompilid sp. 123Arg Ile Arg Leu Gly Leu Trp Asp Gln Leu Ser Arg Leu1 5 10 124 13 PRT Pompilid sp. 124Arg Ile Arg Leu Gly Ile Phe Asp Gln Leu Ser Arg Leu1 5 10 125 13 PRT Pompilid sp. 125Arg Ile Arg Leu Gly Ile Tyr Asp Gln Leu Ser Arg Leu1 5 10 126 13 PRT Pompilid sp. 126Arg Ile Arg Leu Gly Ile Trp Asp Gln Leu Ser Arg Leu1 5 10 127 13 PRT Pompilid sp. 127Arg Leu Lys Ile Gly Leu Phe Asp Gln Leu Ser Arg Leu1 5 10 128 13 PRT Pompilid sp. 128Arg Leu Lys Ile Gly Leu Tyr Asp Gln Leu Ser Arg Leu1 5 10 129 13 PRT Pompilid sp. 129Arg Leu Lys Ile Gly Leu Trp Asp Gln Leu Ser Arg Leu1 5 10 130 13 PRT Pompilid sp. 130Arg Leu Lys Ile Gly Ile Phe Asp Gln Leu Ser Arg Leu1 5 10 131 13 PRT Pompilid sp. 131Arg Leu Lys Ile Gly Ile Tyr Asp Gln Leu Ser Arg Leu1 5 10 132 13 PRT Pompilid sp. 132Arg Leu Lys Ile Gly Ile Trp Asp Gln Leu Ser Arg Leu1 5 10 133 13 PRT Pompilid sp. 133Arg Leu Lys Leu Gly Leu Phe Asp Gln Leu Ser Arg Leu1 5 10 134 13 PRT Pompilid sp. 134Arg Leu Lys Leu Gly Leu Tyr Asp Gln Leu Ser Arg Leu1 5 10 135 13 PRT Pompilid sp. 135Arg Leu Lys Leu Gly Leu Trp Asp Gln Leu Ser Arg Leu1 5 10 136 13 PRT Pompilid sp. 136Arg Leu Lys Leu Gly Ile Phe Asp Gln Leu Ser Arg Leu1 5 10 137 13 PRT Pompilid sp. 137Arg Leu Lys Leu Gly Ile Tyr Asp Gln Leu Ser Arg Leu1 5 10 138 13 PRT Pompilid sp. 138Arg Leu Lys Leu Gly Ile Trp Asp Gln Leu Ser Arg Leu1 5 10 139 13 PRT Pompilid sp. 139Arg Leu Arg Ile Gly Leu Phe Asp Gln Leu Ser Arg Leu1 5 10 140 13 PRT Pompilid sp. 140Arg Leu Arg Ile Gly Leu Tyr Asp Gln Leu Ser Arg Leu1 5 10 141 13 PRT Pompilid sp. 141Arg Leu Arg Ile Gly Leu Trp Asp Gln Leu Ser Arg Leu1 5 10 142 13 PRT Pompilid sp. 142Arg Leu Arg Ile Gly Ile Phe Asp Gln Leu Ser Arg Leu1 5 10 143 13 PRT Pompilid sp. 143Arg Leu Arg Ile Gly Ile Tyr Asp Gln Leu Ser Arg Leu1 5 10 144 13 PRT Pompilid sp. 144Arg Leu Arg Ile Gly Ile Trp Asp Gln Leu Ser Arg Leu1 5 10 145 13 PRT Pompilid sp. 145Arg Leu Arg Leu Gly Leu Phe Asp Gln Leu Ser Arg Leu1 5 10 146 13 PRT Pompilid sp. 146Arg Leu Arg Leu Gly Leu Tyr Asp Gln Leu Ser Arg Leu1 5 10 147 13 PRT Pompilid sp. 147Arg Leu Arg Leu Gly Leu Trp Asp Gln Leu Ser Arg Leu1 5 10 148 13 PRT Pompilid sp. 148Arg Leu Arg Leu Gly Ile Phe Asp Gln Leu Ser Arg Leu1 5 10 149 13 PRT Pompilid sp. 149Arg Leu Arg Leu Gly Ile Tyr Asp Gln Leu Ser Arg Leu1 5 10 150 13 PRT Pompilid sp. 150Arg Leu Arg Leu Gly Ile Trp Asp Gln Leu Ser Arg Leu1 5 10 151 13 PRT Pompilid sp. 151Lys Ile Lys Ile Gly Leu Phe Asp Gln Leu Ser Arg Leu1 5 10 152 13 PRT Pompilid sp. 152Lys Ile Lys Ile Gly Leu Tyr Asp Gln Leu Ser Arg Leu1 5 10 153 13 PRT Pompilid sp. 153Lys Ile Lys Ile Gly Leu Trp Asp Gln Leu Ser Arg Leu1 5 10 154 13 PRT Pompilid sp. 154Lys Ile Lys Ile Gly Ile Phe Asp Gln Leu Ser Arg Leu1 5 10 155 13 PRT Pompilid sp. 155Lys Ile Lys Ile Gly Ile Tyr Asp Gln Leu Ser Arg Leu1 5 10 156 13 PRT Pompilid sp. 156Lys Ile Lys Ile Gly Ile Trp Asp Gln Leu Ser Arg Leu1 5 10 157 13 PRT Pompilid sp. 157Lys Ile Lys Leu Gly Leu Phe Asp Gln Leu Ser Arg Leu1 5 10 158 13 PRT Pompilid sp. 158Lys Ile Lys Leu Gly Leu Tyr Asp Gln Leu Ser Arg Leu1 5 10 159 13 PRT Pompilid sp. 159Lys Ile Lys Leu Gly Leu Trp Asp Gln Leu Ser Arg Leu1 5 10 160 13 PRT Pompilid sp. 160Lys Ile Lys Leu Gly Ile Phe Asp Gln Leu Ser Arg Leu1 5 10 161 13 PRT Pompilid sp. 161Lys Ile Lys Leu Gly Ile Tyr Asp Gln Leu Ser Arg Leu1 5 10 162 13 PRT Pompilid sp. 162Lys Ile Lys Leu Gly Ile Trp Asp Gln Leu Ser Arg Leu1 5 10 163 13 PRT Pompilid sp. 163Lys Ile Arg Ile Gly Leu Phe Asp Gln Leu Ser Arg Leu1 5 10 164 13 PRT Pompilid sp. 164Lys Ile Arg Ile Gly Leu Tyr Asp Gln Leu Ser Arg Leu1 5 10 165 13 PRT Pompilid sp. 165Lys Ile Arg Ile Gly Leu Trp Asp Gln Leu Ser Arg Leu1 5 10 166 13 PRT Pompilid sp. 166Lys Ile Arg Ile Gly Ile Phe Asp Gln Leu Ser Arg Leu1 5 10 167 13 PRT Pompilid sp. 167Lys Ile Arg Ile Gly Ile Tyr Asp Gln Leu Ser Arg Leu1 5 10 168 13 PRT Pompilid sp. 168Lys Ile Arg Ile Gly Ile Trp Asp Gln Leu Ser Arg Leu1 5 10 169 13 PRT Pompilid sp. 169Lys Ile Arg Leu Gly Leu Phe Asp Gln Leu Ser Arg Leu1 5 10 170 13 PRT Pompilid sp. 170Lys Ile Arg Leu Gly Leu Tyr Asp Gln Leu Ser Arg Leu1 5 10 171 13 PRT Pompilid sp. 171Lys Ile Arg Leu Gly Leu Trp Asp Gln Leu Ser Arg Leu1 5 10 172 13 PRT Pompilid sp. 172Lys Ile Arg Leu Gly Ile Phe Asp Gln Leu Ser Arg Leu1 5 10 173 13 PRT Pompilid sp. 173Lys Ile Arg Leu Gly Ile Tyr Asp Gln Leu Ser Arg Leu1 5 10 174 13 PRT Pompilid sp. 174Lys Ile Arg Leu Gly Ile Trp Asp Gln Leu Ser Arg Leu1 5 10 175 13 PRT Pompilid sp. 175Lys Leu Lys Ile Gly Leu Phe Asp Gln Leu Ser Arg Leu1 5 10 176 13 PRT Pompilid sp. 176Lys Leu Lys Ile Gly Leu Tyr Asp Gln Leu Ser Arg Leu1 5 10 177 13 PRT Pompilid sp. 177Lys Leu Lys Ile Gly Leu Trp Asp Gln Leu Ser Arg Leu1 5 10 178 13 PRT Pompilid sp. 178Lys Leu Lys Ile Gly Ile Phe Asp Gln Leu Ser Arg Leu1 5 10 179 13 PRT Pompilid sp. 179Lys Leu Lys Ile Gly Ile Tyr Asp Gln Leu Ser Arg Leu1 5 10 180 13 PRT Pompilid sp. 180Lys Leu Lys Ile Gly Ile Trp Asp Gln Leu Ser Arg Leu1 5 10 181 13 PRT Pompilid sp. 181Lys Leu Lys Leu Gly Leu Phe Asp Gln Leu Ser Arg Leu1 5 10 182 13 PRT Pompilid sp. 182Lys Leu Lys Leu Gly Leu Tyr Asp Gln Leu Ser Arg Leu1 5 10 183 13 PRT Pompilid sp. 183Lys Leu Lys Leu Gly Leu Trp Asp Gln Leu Ser Arg Leu1 5 10 184 13 PRT Pompilid sp. 184Lys Leu Lys Leu Gly Ile Phe Asp Gln Leu Ser Arg Leu1 5 10 185 13 PRT Pompilid sp. 185Lys Leu Lys Leu Gly Ile Tyr Asp Gln Leu Ser Arg Leu1 5 10 186 13 PRT Pompilid sp. 186Lys Leu Lys Leu Gly Ile Trp Asp Gln Leu Ser Arg Leu1 5 10 187 13 PRT Pompilid sp. 187Lys Leu Arg Ile Gly Leu Phe Asp Gln Leu Ser Arg Leu1 5 10 188 13 PRT Pompilid sp. 188Lys Leu Arg Ile Gly Leu Tyr Asp Gln Leu Ser Arg Leu1 5 10 189 13 PRT Pompilid sp. 189Lys Leu Arg Ile Gly Leu Trp Asp Gln Leu Ser Arg Leu1 5 10 190 13 PRT Pompilid sp. 190Lys Leu Arg Ile Gly Ile Phe Asp Gln Leu Ser Arg Leu1 5 10 191 13 PRT Pompilid sp. 191Lys Leu Arg Ile Gly Ile Tyr Asp Gln Leu Ser Arg Leu1 5 10 192 13 PRT Pompilid sp. 192Lys Leu Arg Ile Gly Ile Trp Asp Gln Leu Ser Arg Leu1 5 10 193 13 PRT Pompilid sp. 193Lys Leu Arg Leu Gly Leu Phe Asp Gln Leu Ser Arg Leu1 5 10 194 13 PRT Pompilid sp. 194Lys Leu Arg Leu Gly Leu Tyr Asp Gln Leu Ser Arg Leu1 5 10 195 13 PRT Pompilid sp. 195Lys Leu Arg Leu Gly Leu Trp Asp Gln Leu Ser Arg Leu1 5 10 196 13 PRT Pompilid sp. 196Lys Leu Arg Leu Gly Ile Phe Asp Gln Leu Ser Arg Leu1 5 10 197 13 PRT Pompilid sp. 197Lys Leu Arg Leu Gly Ile Tyr Asp Gln Leu Ser Arg Leu1 5 10 198 13 PRT Pompilid sp. 198Lys Leu Arg Leu Gly Ile Trp Asp Gln Leu Ser Arg Leu1 5 10 199 11 PRT Pompilid sp. MISC_FEATURE (1)..(1) Arg or Lys 199Xaa Xaa Xaa Xaa Gly Xaa Xaa Asp Gln Leu Ser1 5 10 200 10 PRT Pompilid sp. MISC_FEATURE (1)..(1) Arg or Lys 200Xaa Xaa Xaa Xaa Gly Xaa Xaa Asp Gln Leu1 5 10 201 10 PRT Pompilid sp. misc_feature (1)..(1) Arg or Lys 201Xaa Xaa Xaa Xaa Gly Xaa Xaa Asp Gln Xaa1 5 10 202 13 PRT Pompilid sp. 202Arg Ile Lys Ile Gly Leu Phe Asp Gln Leu Ser Lys Leu1 5 10 203 13 PRT Pompilid sp. 203Arg Ile Lys Ile Gly Leu Phe Asp Gln Leu Ser Arg Leu1 5 10

Claims

1. An isolated peptide represented by the following amino acid sequence (SEQ ID NO:201):H-X1-X2-X3-X4-Gly-X6-X7-Asp-Gln-R wherein:each of X1 and X3 independently represents Arg or Lys, each of X2, X4 and X6 independently represents Ile or Leu, and X7 represents Phe, Tyr or Trp; and R represents -Leu-Ser-Lys-Leu-NH2 or -Leu-Ser-Arg-Leu-NH2; and a salt thereof.

2. The isolated peptide as claimed in claim 1 represented by the following amino acid sequence (SEQ ID NO:7):H-X1-X2-X3-X4-Gly-X6-X7-Asp-Gln-Leu-Ser-Lys-Leu-NH2 wherein:each of X1 and X3 independently represents Arg or Lys, each of X2, X4 and X6 independently represents Ile or Leu, and X7 represents Phe, Tyr or Trp; and a salt thereof.

3. The isolated peptide as claimed in claim 1 represented by the following amino acid sequence (SEQ ID NO:8):H-X1-X2-X3-X4-Gly-X6-X7-Asp-Gln-Leu-Ser-Arg-Leu-NH2 wherein:each of X1 and X3 independently represents Arg or Lys, each of X2, X4 and X6 independently represents Ile or Leu, and X7 represents Phe, Tyr or Trp; and a salt thereof.

4. The isolated peptide as claimed in claim 1 represented by the following amino acid sequence (SEQ ID NO:202):H-Arg-Ile-Lys-Ile-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Lys-Leu-NH2 and a salt thereof.

5. The isolated peptide as claimed in claim 1 represented by the following amino acid sequence (SEQ ID NO:203):H-Arg-Ile-Lys-Ile-Gly-Leu-Phe-Asp-Gln-Leu-Ser-Arg-Leu-NH2 and a salt thereof.

6. The isolated peptide and a salt as claimed in claim 1 as a glutamate receptor agonist.