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Published on:January 2017
Indian Journal of Pharmaceutical Education and Research, 2017; 51(1):43-50
Original Article | doi:10.5530/ijper.51.1.7

Optimizing the Amino Acid Sequences of Peptides and Improving Their Specificity of Binding to SH3 Domains of Target Proteins


Authors and affiliation (s):

Yanrong Ren1, Qiang Wang1, Xiaobo Li2

1School of Biological and Chemical Engineering, Chongqing University of Education, Chongqing 400067, P. R. China

2Human Resources Office, Chongqing University of Education, Chongqing 400067, P. R. China

Abstract:

Introduction: It is always a crucial challenge in biotechnology to avoid promiscuous binding between an anticancer peptide and multiple SH3 domains, thus reducing potential toxic effects. In spite of a great deal of experimental efforts, the association between amino acid sequence and binding specificity of peptide remained largely unknown. Aim: The purpose of this study was to optimize the amino acid sequence of peptide ligands and render high specificity towards designated therapeutic targets. Results: By exploring peptide ligands in MINT database and utilizing SH3PepInt tool for in silico peptide-target binding, here we investigated how the amino acid sequence of a peptide determined its specificity of binding to the SH3 domain of c-Src protein. We found that the 5th and the 6th residues of proline-rich motif had large influence on peptide-target binding. By purposely modifying the amino acid at these two key positons, the overall level of binding promiscuity was significantly reduced. Conclusion: Taken together, these findings corroborated that the SH3 domain of c-Src protein can discern subtle differences in the amino acid sequence of ligands, which provided a unique opportunity for rational design of therapeutic peptides.

Key words: SH3 domain, c-Src, Promiscuity, Specificity, Peptide rational design

 

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The Official Journal of Association of Pharmaceutical Teachers of India (APTI)
(Registered under Registration of Societies Act XXI of 1860 No. 122 of 1966-1967, Lucknow)

Indian Journal of Pharmaceutical Education and Research (IJPER) [ISSN-0019-5464] is the official journal of Association of Pharmaceutical Teachers of India (APTI) and is being published since 1967.

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IJPER uses reference linking service using Digital Object Identifiers (DOI) by Crossref. Articles from the year 2013 are being assigned DOIs for its permanent URLs