title: Novel peptide inhibitors for Grb2 SH2 domain and their detection by surface plasmon resonance.
abstract: One of the critical intracellular signal transduction pathways involves the binding of the Grb2 SH2 domain to the phosphotyrosine (pTyr) motifs on growth factor receptors, such as epidermal growth factor receptor (EGFR) and erbB2, leading to downstream activation of the oncogenic Ras signaling pathway. Therefore, the Grb2 SH2 domain has been chosen as our target for the development of potential anticancer agents. As a continuation of our earlier work, herein we report the design and synthesis of new peptide analogs, and their inhibitory effect on the Grb2 SH2 domain using surface plasmon resonance (SPR) technology. These novel agents do not contain phosphotyrosine or phosphotyrosine mimics. Binding interactions between these peptides and the Grb2 SH2 domain were measured and analyzed using a BIAcore X instrument, which provides detailed information on the real-time detection of the binding interaction. The results of this study should provide important information for the further development of peptides or peptidomimetics with high affinity for the Grb2 SH2 domain.
authors.affiliation: Department of Nutrition, China Medical College, Taichung 404, Taiwan. fdlung@mail.cmc.edu.tw
authors.forename: F-D T
authors.initials: FD
authors.lastname: Lung
authors.forename: J-Y
authors.initials: JY
authors.lastname: Tsai
authors.forename: S-Y
authors.initials: SY
authors.lastname: Wei
authors.forename: J-W
authors.initials: JW
authors.lastname: Cheng
authors.forename: C
authors.initials: C
authors.lastname: Chen
authors.forename: P
authors.initials: P
authors.lastname: Li
authors.forename: P P
authors.initials: PP
authors.lastname: Roller
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D001710:Biotin / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000378:metabolism; D051380:GRB2 Adaptor Protein; D020128:Inhibitory Concentration 50; D007700:Kinetics; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D011506:Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016339:Spectrometry, Mass, Fast Atom Bombardment; D020349:Surface Plasmon Resonance; D018909:src Homology Domains
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004791:Enzyme Inhibitors; D051380:GRB2 Adaptor Protein; D010455:Peptides; D011506:Proteins; D001710:Biotin