Claims
- 1. A method for cardioprotection in an individual which comprises administering a therapeutically effective amount of an active agent to an individual in need of cardioprotection as a result of said individual suffering from a condition of hypoxia, anoxia or ischemia, said active agent selected from the group consisting of:(a) contulakin-G comprising the amino acid sequence Xaa1-Ser-Glu-Glu-Gly-Gly-Ser-Asn-Ala-Thr-Lys-Lys-Xaa2-Tyr-Ile-Leu (SEQ ID NO:1), where Xaa1 is pyro-Glu, Xaa2 is proline or hydroxyproline and T10 is modified to contain an O-glycan; (b) a generic contulakin-G having the following general formula Xaa1-Xaa2-Xaa3-Xaa3-Gly-Gly-Xaa2-Xaa4-Xaa5-Xaa6-Xaa7-Xaa8-Xaa7-Xaa9-Xaa10-Ile-Leu (SEQ ID NO:2), where Xaa1 is pyro-Glu, Glu, Gln or γ-carboxy-Glu; Xaa2 is Ser, Thr or S-glycan modified Cys; Xaa3 is Glu or γ-carboxy-Glu; Xaa4 is Asn, N-glycan modified Asn or S-glycan modified Cys; Xaa5 is Ala or Gly; Xaa6 is Thr, Ser, S-glycan modified Cys, Tyr or any hydroxy containing synthetic amino acid; Xaa7 is Lys, N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys, Arg, omithine, hornoarginine or any synthetic basic amino acid; Xaa8 is Ala, Gly, Lys, N-methyl-Lys, N,N-dimethyl-Lys, N,N,N-trimethyl-Lys, Arg, omithine, homoarginine, any synthetic basic amino acid or X-Lys where X is (CH2)n, phenyl, —(CH2)m—(CH═CH)—(CH2)mH or —(CH2)m—(C≡C)—(CH2)mH in which n is 1-4 and m is 0-2; Xaa, is Pro or hydroxy-Pro; and Xaa10 is Tyr, mono-iodo-Tyr, di-Iodo-Tyr, O-sulpho-Tyr, O-phospho-Tyr, nitro-Tyr, Trp, D-Trp, bromo-Trp, bromo-D-Trp, chloro-Trp, chloro-D-Trp, Phe, L-neo-Trp, or any synthetic aromatic amino acid, with the proviso that the generic contulakin-G is not desglycosylated contulakin-G; (c) a generic contulakin-G of (b) which is modified to contain an O-glycan, an S-glycan or an N-glycan; (d) a contulakin-G analog which comprises an N-terminal truncation of from 1 to 9 amino acids of the generic contulakin-G of (b); (e) a contulakin-G analog of (c), wherein an Ser-O-glycan, Thr-O-glycan or Cys-S-glycan is substituted for the amino acid residue at the truncated N-terminus; (f) a contulakin-G analog of (c), wherein an Ser-O-glycan, Thr-O-glycan or Cys-S-glycan is substituted for a residue at positions 2-9 of the generic contulakin-G; and (g) a contulakin-G analog which comprises an N-terminal truncation of 10 amino acids of the generic contulakin-G of (b) which is further modified to contain a Lys-N-glycan at residue 11 of the generic contulakin-G.
- 2. The method of claim 1 wherein the glycan is Gal(β1→3)GalNAc(α1→).
- 3. The method of claim 1 wherein the glycan has the structure shown in FIG. 3, wherein R1 is an amino capable of being derivatized with a gylcan either chemically or enzymatically; R2 is OH, NH2, NHSO3Na, NHAc, O-sulphate, O-phosphate, or O-glycan; R3 is H, SO3, PO3, acetyl, sialic acid or monosaccharide; R4 is H, SO3, PO3, acetyl or monosaccharide; R5 is OH, NH2, NHSO3Na, NHAc, O-sulphate, O-phosphate, O-monosaccharide or, O-acetyl; R6 is H, SO3, PO3, acetyl or monosaccharide; R7 is H, SO3, PO3, acetyl or monosaccharide; R8 is H, SO3, PO3, acetyl or monosaccharide; n is 0-4 and m is 1-4.
- 4. The method of claim 1, wherein said cardioprotection in said individual suffering from a condition of hypoxia, anoxia or ischemia is for treating conditions associated with vascular accident, myocardial infarct, angina, surgery, coronary artery bypass graft surgery (CABG), percutaneous transluminal angioplasty (PTCA), physical trauma, non-fatal drowning, non-fatal suffocation, perinatal asphyxia or hypoglycemic events.
CROSS-REFERENCE TO RELATED APPLICATIONS
The present application is a continuation-in-part application of U.S. patent application Ser. No. 09/606,247 filed on Jun. 29, 2000, which in turn is a divisional application of U.S. patent application Ser. No. 09/420,797 filed Oct. 19, 1999, now U.S. Pat. No. 6,369,193, each incorporated herein by reference. The present application is also related to U.S. provisional patent applications Serial No. 60/105,015, filed on Oct. 20, 1998, Ser. No. 60/128,561, filed on Apr. 9, 1999 and Ser. No. 60/130,661, filed on Apr. 23, 1999, each incorporated herein by reference, and claims priority to each under 35 USC §119(e).
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Provisional Applications (3)
|
Number |
Date |
Country |
|
60/105015 |
Oct 1998 |
US |
|
60/128561 |
Apr 1999 |
US |
|
60/130661 |
Apr 1999 |
US |
Continuation in Parts (1)
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Number |
Date |
Country |
Parent |
09/606247 |
Jun 2000 |
US |
Child |
09/609534 |
|
US |