Tunghai University Institutional Repository:Item 310901/21312
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    Please use this identifier to cite or link to this item: http://140.128.103.80:8080/handle/310901/21312


    Title: Small nonphosphorylated Grb2-SH2 domain antagonists evaluated by surface plasmon resonance technology
    Authors: Lung, F.-D.T.?,?Chang, C.-W.,?Chong, M.-C.,?Liou, C.-C.,?Li, P.,?Peach, M.L.,?Nicklaus, M.C.,?Lou, B.-S.,?Roller, P.P.
    Contributors: Department of Chemistry, Tunghai University
    Keywords: BIACORE X;Grb2;Peptides;Ras;SH2 domain;Signal transduction pathway;Surface plasmon resonance
    Date: 2005
    Issue Date: 2013-05-14T09:04:47Z (UTC)
    Abstract: The growth factor receptor-binding protein-Src homology 2 (Grb2-SH2) domain plays an important role in the oncogenic Ras signal transduction pathway, which involves cell proliferation and differentiation. Therefore, the Grb2-SH2 domain has been chosen as our target for development of potential antiproliferative agents. Herein, we report the study of the inhibitory effects of small nonphosphorylated peptide analogs interacting with the Grb2-SH2 domain protein by surface plasmon resonance (SPR) technology. A set of 8 related peptide analogs were synthesized, purified, and characterized. Their inhibitory effects on Grb2-SH2 were evaluated by the SPR technology developed with the BIACORE X instrument. The lead peptide, Fmoc-Glu-Tyr-Aib-Asn-NH 2 (Fmoc-E-Y-Aib-N; Fmoc: 9-fluorenylmethyoxycarbonyl; Aib = α-amino isobutyric acid) inhibited Grb2-SH2 domain function with an IC 50 value of 8.7 μM. A molecular modeling study of the lead peptide indicated that the glutamate in the Fmoc peptide is ideally positioned to form a strong salt bridge to Arg 67 in the Grb2-SH2 domain, using both its backbone carbonyl and its acidic group. Residue Glu 89 in Grb2-SH2 flips inward to fill the binding site and partially replace the phosphate group as a hydrogen-bond acceptor. Results of these studies provide important information for further development of potent nonphosphorylated peptide inhibitors of the Grb2-SH2 domain. ? 2005 Wiley Periodicals, Inc.
    Relation: Biopolymers - Peptide Science Section 80 (5) , pp. 628-635
    Appears in Collections:[Department of Chemistry ] Periodical Articles

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