Poster abstracts

Poster number 85 submitted by Yanyan Zhang

Understanding the biology of SH2 domains via a combinatorial chemistry approach

Yanyan Zhang (Chemistry), Dehua Pei (Chemistry)

Abstract:
Src homology-2 (SH2) domains are small modular domains of approximately 100 amino acids. They play an essential role in the regulation of many signaling pathways by binding to phosphotyrosine (pY)-containing proteins and promoting the formation of protein complexes. In this work, a combinatorial peptide library method was employed to identify the sequence specificities of the SH2 domains in suppressor of cytokine signaling (SOCS) proteins. The resulting consensus motifs will be used to search against protein databases for potential physiological binding partners. In addition, a cylcic peptide library was screened against the SH2 domain of growth factor receptor-bound protein 2 (Grb2). Potent Grb2 SH2 antagonists were identified and were shown to inhibit the growth of human breast cancer cells. Our system should be readily applied to any modular domains that recognize short peptide motifs for the identification of cellular binding partners and potent cyclic peptide inhibitors.

Keywords: SH2 domain, combinatorial chemistry, cyclic peptidyl inhibitor