Discovery of thioether-bridged cyclic pentapeptides binding to Grb2-SH2 domain with high affinity.

ABSTRACT: Blocking the interaction between phosphotyrosine (pTyr)-containing activated receptors and the Src homology 2 (SH2) domain of the growth factor receptor-bound protein 2 (Grb 2) is considered to be an effective and non-cytotoxic strategy to develop new anti-proliferate agents due to its potential to shut down the Ras activation pathway. In this study, a series of phosphotyrosine containing cyclic pentapeptides were designed and synthesized based upon the phage library derived cyclopeptide, G1TE. A comprehensive SAR study was also carried out to develop potent Grb2-SH2 domain antagonists based upon this novel template. With both the peptidomimetic optimization of the amino acid side-chains and the constraint of the backbone conformation guided by molecular modeling, we developed several pote

SUBMITTER: Jiang S 

PROVIDER: S-EPMC7291730 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature