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

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 5