Synthesis and structure-activity relationships of linear and conformationally constrained peptide analogues of CIYKYY as Src tyrosine kinase inhibitors

J Med Chem. 2006 Jun 1;49(11):3395-401. doi: 10.1021/jm060334k.

Abstract

A series of peptide analogues of Ac-CIYKYY (1) were synthesized by functional group modifications in peptide side chains or by introducing conformational constraints, to improve the inhibitory potency against active Src kinase. Ac-CIYKF(4-NO2)Y (2, IC50 = 0.53 microM) and conformationally constrained peptide 31 (IC50 = 0.28 microM) exhibited 750- and 1400-fold higher inhibitory activities, respectively, versus that of 1 (IC50 = 400 microM). Compound 2 exhibited a partial competitive inhibition pattern against ATP.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / antagonists & inhibitors
  • Adenosine Triphosphate / chemistry
  • Oligopeptides / chemical synthesis*
  • Oligopeptides / chemistry
  • Protein Conformation
  • Proto-Oncogene Proteins pp60(c-src) / antagonists & inhibitors
  • Proto-Oncogene Proteins pp60(c-src) / chemistry
  • Structure-Activity Relationship
  • src-Family Kinases / antagonists & inhibitors*

Substances

  • Oligopeptides
  • Adenosine Triphosphate
  • Proto-Oncogene Proteins pp60(c-src)
  • src-Family Kinases