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Literature DB >> 10395476

Structure-based design, synthesis, and X-ray crystallography of a high-affinity antagonist of the Grb2-SH2 domain containing an asparagine mimetic.

P Furet¹, C García-Echeverría, B Gay, J Schoepfer, M Zeller, J Rahuel.

Abstract

Previous efforts in the search for molecules capable of blocking the associations between the activated tyrosine kinase growth factor receptors and the SH2 domain of Grb2 had resulted in the identification of 3-amino-Z-pTyr-Ac6c-Asn-NH2, a high-affinity and selective antagonist of this SH2 domain. In the present paper, we report the successful replacement of asparagine in this compound by a beta-amino acid mimetic, which brings us closer to our objective of identifying a Grb2-SH2 antagonist suitable for pharmacological investigations.

Entities: Chemical Gene

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Year: 1999 PMID： 10395476 DOI： 10.1021/jm991013u

Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446

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Cited

6 in total

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Journal: Protein Sci Date: 2000-12 Impact factor: 6.725

2. Conformationally constrained peptidomimetic inhibitors of signal transducer and activator of transcription. 3: Evaluation and molecular modeling.

Authors: Pijus K Mandal; Donald Limbrick; David R Coleman; Garrett A Dyer; Zhiyong Ren; J Sanderson Birtwistle; Chiyi Xiong; Xiaomin Chen; James M Briggs; John S McMurray
Journal: J Med Chem Date: 2009-04-23 Impact factor: 7.446

Structure-based design, synthesis, and X-ray crystallography of a high-affinity antagonist of the Grb2-SH2 domain containing an asparagine mimetic.

1. Rationale for Bcl-xL/Bad peptide complex formation from structure, mutagenesis, and biophysical studies.

2. Conformationally constrained peptidomimetic inhibitors of signal transducer and activator of transcription. 3: Evaluation and molecular modeling.

3. Solution structure of the Grb2 SH2 domain complexed with a high-affinity inhibitor.

4. Computer applications for prediction of protein-protein interactions and rational drug design.

5. Synthesis and structural characterization of a monocarboxylic inhibitor for GRB2 SH2 domain.

6. Development of Grb2 SH2 Domain Signaling Antagonists: A Potential New Class of Antiproliferative Agents.