PEPTIDES FOR ACTIVATION OF ANGIOGENESIS, PHARMACEUTICAL COMPOUNDS CONTAINING SAME AND USE OF THESE COMPOUNDS

摘要

The invention provides novel peptides of formula (I) and their salts or metal complexes R0- R1- Q(X) - R2- R3 (I) - wherein the main substituent meanings are as follows: Q represents Lys, Cys or Ser; X is H, Bzl, R0, R0-Tyr-Pro-Asp-Glu-Ile-Glu-Tyr-Ile-Phe, R0- Ile-Lys-Pro-His- Gln-Gly-Gln, or R0- Gly-Val-Ser-Ser-Ser-Ser, R₀ stands for H or NH2-protecting groups commonly used in peptide chemistry, R₁ is Trp, D-Trp, Phe, D-Phe, ß-Asp(a-Dopa), ß-Asp(a-Ind), Tyr-Pro-Asp- Glu-Ile-Glu-Tyr-Ile-Phe, Ile-Lys-Pro-His-Gln-Gly-Gln, Pro-Glu-Ser-Thr- Asn-Leu, Gly-Val-Ser-Ser-Ser-Ser, or a valency bond, R₂ represents Gly, Asn-Asp-Glu-Gly-Leu-Glu-(Gly) n, Asp-Asp-Gly-Gln-Ile-(Gly) n, His, Ser, Cpa, Dopa, Tyr, Thr, Pro, Trp-Ser, Phe-Ser, 2-aminophenyl-, or Cys(X2), wherein X2 is Acm, Bzl or an SH-protecting group commonly used in peptide chemistry, and R₃ is OH, OMe, NH2, or amide substituted by one or two identical or different C1-C6 alkyl group(s), Thr-NH2, or Tyr-OMe. The invention further provides pharmaceutical compositions containing these peptides with the ability of stimulating angiogenesis and vascularization. The invention further relates to the use of these compounds for preparing pharmaceutical compositions for treatment of injured tissues such as chronic wounds, heart tissues injured by ischemia or heart attack, and neural tissues injured by stroke. The invention also relates to a method for preparing tissue samples for testing angiogenesis-inhibiting agents.