Identification And Development Of Chemical Probes Targeting Growth Factor Receptor-Bound Protein 2 (Grb-2)

Abstract

Grb2 is an essential signaling adaptor protein that takes an extraordinary place to regulate the enzymatic activity intercellularly. It can maintain the intercellular reactivities through its interaction with receptor tyrosine kinases (RTKs). Grb2 contains two domains called Src homology 3 (SH3) and one domain named Src homology 2 (SH2). In cell membrane, Grb2-SH3 domain is binding to the target effectors, whilst the Grb2-SH2 domain is binding to receptors. Grb2-SH2 domain has critical roles in binding to peptides containing phosphotyrosine (pY). Whereas Grb2-SH3 domain assists the activation of the cyclic process of the Ras-GTPase from Ras-GDP to Ras-GTP. The research goal is to identify and the development of novel non-peptide small molecules associated with Grb2 and tests them on mice. The various Grb2 complexes provide specific information to study the properties on the binding site of Grb2. This leads to the shut down of oncogenic pathways and thus prevent hyperproliferative diseases.