Preparation of functional polypeptides via methionine alkylation

多肽是化学合成的天然蛋白质的模拟物，作为医用生物材料的模拟物具有许多优点。由于它们是合成的，这些材料不含可能具有不良性质的生物杂质，并且制备时不含可能在生物衍生材料中携带的病原体。多肽的化学修饰是一种提高这些材料性能的方法，最终可用于诸如药物输送载体、再生医学支架或医疗诊断设备等应用。本研究项目的重点是改进目前的化学多肽修饰技术，使这些工艺更经济、范围更广。预计该项目的成功将提供一般方法，可用于下游一些重要的医学应用。在这个项目中，加州大学洛杉矶分校的Timothy Deming教授计划纳入代表性不足的群体，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。在美国国家科学基金会化学部大分子、超分子和纳米化学项目的支持下，戴明教授进行了以下研究：(1)开发实用的、选择性的方法来化学修饰多肽，以及(2)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蛋氨酸残基的反应，以制备乙酰化蛋氨酸磺酸衍生物。该项目的关键挑战是确定烷基化试剂结构如何影响所得蛋氨酸磺酸基的化学性质和稳定性。从这些研究中获得的知识可以对多肽官能团的反应性进行微调，这可能对下游特定用途有价值，例如在药物的控制释放中，并有望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.