Development of Grb2 SH2 Domain Signaling Antagonis

Authors: Terrence R Burke

Publish Date: 2006/03/14

Volume: 12, Issue: 1, Pages: 33-48

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Abstract

Aberrant signaling through proteintyrosine kinase PTKdependent pathways is associated with several proliferative diseases Accordingly PTK inhibitors are being developed as new approaches for the treatment of certain cancers Growth factor receptor bound protein 2 Grb2 is an important downstream mediator of PTK signaling that serves obligatory roles in many pathogenic processes One of the primary functions of Grb2 is to bind to specific phosphotyrosyl pTyrcontaining sequences through its Src homology 2 SH2 domain Agents that bind to the Grb2 SH2 domain and prevent its normal function could disrupt associated PTK signaling and serve as alternatives to kinasedirected inhibitors Starting from the Xray crystal structure of a lead peptide bound to the Grb2 SH2 domain this review will summarize important contributions to these efforts The presentation will be thematically arranged according to the region of peptide modified proceeding from the Nterminus to the Cterminus with a special section devoted to aspects of conformational constraint

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