Peptide compositions with growth factor-like activity

Details Peptide compositions with growth factor-like activity Peptide compositions with growth factor-like activity

C - Chemistry, Metallurgy

07

K

C07K 7/06 (2006.01) A61K 38/08 (2006.01) A61K 38/18 (2006.01) A61K 47/00 (2006.01) C07K 14/495 (2006.01)

Patent

CA 2269655

Small peptide mimics of TGF-.beta., having the gen-eral sequence AA j-AA j+1-AA j+2 followed by AA i+n shortly thereafter, have been prepared. In this se-quence, AA i is alanine, asparagine, or leucine, AA i+1 is valine or isoleucine, AA i+2 is alanine, n is 3, 4 or such that there are n-3 amino acid residues in be-tween AA j+2 and AA i+n, and AA j+n is glutamic acid, aspartic acid, glutamine or asparagine. Because the es-sential requirement for TGF-.beta. activity is the peptide's ability to form a stable .beta.-bend structure under physio-logic conditions, the inventive peptides are collectively referred to as .beta.-bend peptides. Compositions for ap-plications such as tissue repair are also provided that comprise a biocompatible matrix having cytomodulin or a cytomodulin analog admixed with or carried by the matrix.

Cette invention se rapporte à la préparation de petits analogues peptidiques du TGF- beta , représentés par la séquence générale AAj-AAj+1-AAj+2 suivie de près par AAi+n. Dans cette séquence, AAi est alanine, aspargine ou leucine, AAi+1 est valine ou isoleucine, AAi+2 est alanine, n est égal à 3, 4 ou 5 de telle sorte que n-3 restes d'acides aminés sont placés entre AAj+2 et AAi+n, et AAj+n est acide glutamique, acide aspartique, glutamine ou asparagine. Etant donné que l'activité du TGF- beta se caractérise principalement par la capacité du peptide à former une structure de type coude beta stable dans des conditions physiologiques, les peptides de l'invention sont désignés collectivement par le terme de peptides à coude beta . L'invention se rapporte également à des compositions conçues pour des applications telles que la réparation tissulaire, lesdites compositions comportant de la cytomoduline ou un analogue de cytomoduline mélangé à la matrice ou portée par cette dernière.

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