Preparation of functional polypeptides via methionine alkylation

多肽是天然蛋白质的化学合成模拟物，并且作为用于医学用途的生物材料的模拟物提供许多优点。 由于它们是合成的，因此这些材料不含可能具有不良性质的生物杂质，并且制备时也不含生物衍生材料中可能携带的病原体。 多肽的化学修饰是增强这些材料的性质以最终用于诸如药物递送载体、再生医学支架或作为医学诊断装置的应用的方法。 该研究项目的重点是改进目前化学多肽修饰的最新技术，使这些方法更经济，范围更广。 预计该项目的成功将提供可用于下游许多医学重要应用的通用方法。 在这个项目中，加州洛杉矶大学的蒂莫西德明教授计划将代表性不足的群体包括在内，教授和培训研究生和本科生，并在出版物和演讲中传播研究成果。 在NSF化学部的大分子、超分子和纳米化学项目的支持下，德明教授进行了以下研究：（i）开发实用的、选择性的方法来化学修饰多肽，以及（ii）开发这种化学方法来控制多肽分子的附着和释放。 更具体地说，他的研究小组计划探索和开发多肽中甲硫氨酸残基的反应，以制备烷基化甲硫氨酸锍衍生物。 该项目的关键挑战是确定烷基化试剂结构如何影响所得甲硫氨酸锍基团的化学性质和稳定性。 从这些研究中获得的知识可以允许对多肽官能团反应性进行微调，这对于下游特定用途（例如药物的控释）可能是有价值的，并且预计将为开发一类新的功能性生物聚合物奠定基础。

Polypeptides are chemically synthesized mimics of natural proteins, and offer many advantages as mimics of biological materials for medical uses. Since they are synthetic, these materials are free from biological impurities that may have undesirable properties, and also are prepared free from pathogens that may be carried in biologically derived materials. Chemical modification of polypeptides is a method to enhance the properties of these materials for eventual use in applications such as drug delivery vehicles, regenerative medicine scaffolds, or as medical diagnostic devices. This research project is focused on improving upon the current state of the art for chemical polypeptide modification to make these processes more economical and broader in scope. Success of this project is expected to provide general methods that may be used downstream in a number of medically important applications. In this project, Prof. Timothy Deming at the University of California Los Angeles plans to include underrepresented groups, teach and train graduate and undergraduate students, and disseminate research findings in publications and presentations. Under the support of the Macromolecular, Supramolecular and Nanochemistry Program of the NSF Division of Chemistry, Prof. Deming conducts research to (i) develop practical, selective methods to chemically modify polypeptides, and (ii) develop this chemistry for controlled attachment and release of molecules from polypeptides. More specifically, his research group plans to explore and develop the reactions of methionine residues in polypeptides to prepare aklylated methionine sulfonium derivatives. The key challenge of this project is to determine how alkylating reagent structure affects the chemistry and stability of the resulting methionine sulfonium groups. The knowledge gained from these studies can allow fine tuning of polypeptide functional group reactivity that may be valuable for downstream specific uses, e.g. in the controlled release of drugs, and is expected to lay groundwork for development of a new class of functional biopolymers.