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

1, 1, 2

  1. 1School of Biological and Chemical Engineering, Chongqing University of Education, Chongqing 400067, P. R. China.
  2. 2Human Resources Office, Chongqing University of Education, Chongqing 400067, P. R. China.

CORRESPONDENCE

Yanrong Ren

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

ren_sci@sina.com

Received: 30-09-2016; Accepted: 28-11-2016.

Volume 51, Issue 1 · pp. 43-50 · 2017 · DOI: 10.5530/ijper.51.1.7

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.

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    Ren, Y., Wang, Q., & Li, X. (2017). Optimizing the Amino Acid Sequences of Peptides and Improving Their Specificity of Binding to SH3 Domains of Target Proteins. Indian Journal of Pharmaceutical Education and Research, 51(1), 43-50. https://doi.org/10.5530/ijper.51.1.7

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    © 2017 Author(s)

    This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 License, which permits unrestricted use, distribution and reproduction in any medium, provided the original author and source are credited. CC BY 4.0