Format

Send to

Choose Destination
J Med Chem. 2004 Jun 3;47(12):3131-41.

Conformationally constrained peptide analogues of pTyr-Glu-Glu-Ile as inhibitors of the Src SH2 domain binding.

Author information

1
Department of Biomedical Sciences, University of Rhode Island, Kingston, RI 02881, USA.

Abstract

A series of conformationally constrained peptides were designed and synthesized as the Src SH2 domain ligands based on a tetrapeptide sequence pTyr-Glu-Glu-Ile (pYEEI). In general, the constrained peptides such as compounds 6, 7, and 11 (IC(50) = 1.1-1.5 microM) showed higher binding affinities to the Src SH2 domain relative to the corresponding linear peptides 8a, 9a, and 13a, respectively (IC(50) > 100 microM), and pYEEI (IC(50) = 6.5 microM), as evaluated by a fluorescence polarization assay. Molecular modeling studies revealed that in constrained peptides, the isoleucine side chain penetrates very deeply into the hydrophobic binding pocket (P + 3 site) of the Src SH2 domain. These constrained peptides can serve as novel templates for the design of small and nonpeptidic inhibitors of the Src SH2 domain.

PMID:
15163193
DOI:
10.1021/jm040008+
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for American Chemical Society
Loading ...
Support Center