多肽序列优化降低c-Src蛋白靶向药物的毒性风险

发布时间：2018-06-23 17:04

本文选题：c-Src蛋白 + SH结构域　；参考：《重庆大学学报》2017年03期

【摘要】：避免c-Src蛋白的多肽类拮抗剂与多个蛋白发生混杂性结合,对于降低抗癌药物的毒性风险具有重要作用。本研究运用生物信息学方法对氨基酸序列进行优化设计,旨在减少混杂性结合的发生。本研究综合利用各种多肽数据库和生物信息学工具,首先总结了多肽分子与多个蛋白SH3结构域之间潜在的混杂性结合,并发现了其中的内在规律。随后,根据所发现的规律,对多肽的氨基酸序列进行针对性的优化设计。结果表明,大多数多肽在经过优化后,所结合的c-Src以外的蛋白数量都有所下降,从而显著提高了多肽与c-Src蛋白之间结合的特异性(P0.05),并降低了其潜在的毒性风险。本研究所取得的结果将为设计具有高度特异性和低毒性的靶向性多肽药物提供参考。
[Abstract]:To avoid the hybrid binding of c-Src protein antagonists with multiple proteins, it is important to reduce the risk of toxicity of anticancer drugs. The aim of this study was to reduce the occurrence of hybrid binding by using bioinformatics to optimize the design of amino acid sequences. In this study, using various polypeptide databases and bioinformatics tools, we first summarized the potential hybrid binding between polypeptide molecules and multiple protein SH3 domains, and found the inherent law. Then, the amino acid sequence of polypeptide was optimized according to the law found. The results showed that the number of proteins other than c-Src was decreased after the optimization of most peptides, which significantly increased the specificity of binding between the peptides and c-Src protein (P0.05), and reduced its potential toxicity risk. The results of this study will provide a reference for the design of targeted polypeptide drugs with high specificity and low toxicity.
【作者单位】：重庆第二师范学院生物与化学工程系;重庆第二师范学院人事处;
【基金】：重庆市科委前沿与应用基础研究计划项目(cstc2014jcyjA10104) 重庆第二师范学院校级科研创新团队(KYC-cxtd03-2017004) 第二批重庆市高等学校青年骨干教师资助计划~~
【分类号】：R96

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