CAREER: Macromolecular glycosidase mimics

在美国国家科学基金会有机和大分子化学项目的CAREER奖的支持下，奥本大学化学系的Susanne Striegler教授将专注于通过检测模板微凝胶作为催化剂来开发一种选择性糖基化的新方法。这些研究计划利用具有挑战性的糖苷和金属配合物的合成，并将采用抑制试验来提供设计的过渡态类似物作为酶抑制剂的重要信息。现代光谱和量热方法将应用于提供合成的过渡态类似物与铜（II）配合物之间的配位行为的基本见解。乳液聚合将被用来固定氮氮糖苷-金属络合物组装成模板微凝胶，将作为可溶性，均相催化剂的功能。所得材料将通过动力学实验进行表征，以探测金属配合物加速糖苷解理，即糖基向水的转移。本研究结果将为替代传统合成和酶促方法的新型大分子催化剂的开发提供基础，并为具有潜在药理作用的糖缀合物的合成开辟新的方向。凭借这一职业奖，Stiegler教授将大大提高目前对过渡态类似物的了解，这些类似物既可以作为酶的抑制剂，也可以作为制备高级合成材料的模板。正在为开发复杂的大分子催化剂奠定基础，这种催化剂可以将糖基部分转移到除水以外的复杂受体上。这些研究也为基于配位键制备高效的大分子酶模拟物开辟了新的研究方向。实验演示迷你课程将突出化学的优点，并提供与日常生活的联系。对一种可见现象的解释将激发观众对科学的兴趣，这些观众将包括来自附近历史悠久的黑人高中和大学的学生，如布洛克县高中或塔斯基吉大学，他们的老师和指导员，以及其他感兴趣的公众成员。PI实验室的研究机会包括暑期研究项目和为当地高中学生提供的短期有机合成课程。将提供有机化学的实践经验和交流机会，以进一步表明学生对化学职业的兴趣。参与本课程的研究生和本科生将在化学和生物学的界面进行培训。他们将获得进行有机合成（包括聚合）的技能，进行配位事件的光谱和量热表征，并确定酶和合成催化剂的动力学特征。此外，他们还将参与面向公众的外展项目，特别关注阿拉巴马州农村地区的非洲裔美国学生。

With the support of this CAREER Award from the Organic and Macromolecular Chemistry Program at the National Science Foundation, Professor Susanne Striegler, of the Department of Chemistry at Auburn University will focus on developing a novel method for selective glycosylation by examining templated microgels as catalysts. The studies planned utilize challenging syntheses of glycosides and metal complexes, and will employ inhibition assays to provide crucial information on the use of the designed transition state analogues as enzyme inhibitors. Modern spectroscopic and calorimetric methods will be applied to provide fundamental insights into the coordination behavior between the synthesized transition state analogues and copper(II) complexes. Emulsion polymerization will be employed to immobilize the azaglycoside-metal complex assemblies into templated microgels that will function as soluble, homogenous catalysts. The material obtained will be characterized by kinetic experiments to probe the metal complex accelerated glycoside cleavage, i.e. glycosyl transfer to water. The results of this study will provide the foundation for novel macromolecular catalysts as an alternative to conventional syntheses and enzymatic approaches and open new directions towards the synthesis of glycoconjugates with prospective pharmacological effect. With this CAREER award Professor Stiegler will significantly enhance the current knowledge on transition state analogues to act as both inhibitors of enzymes and templates for the preparation of advanced synthetic materials. Foundations are being laid for the development of sophisticated macromolecular catalysts, which transfer glycosyl moieties to complex acceptors other than water. The studies proposed also open new research directions for the preparation of efficient, macromolecular enzyme mimics based on coordinative bonds. The experimental demonstration mini-course will highlight the merits of chemistry and provide connections to daily life. Explanations of a visible phenomenon will spark interest for sciences in an audience that will include students from nearby, historically black high schools and colleges, e.g. Bullock County High School or Tuskegee University, their teachers and instructors, and other interested members of the public. Research opportunities in the PI's laboratory include a summer research project and a short organic synthesis course for students from local high schools. Hands-on experience in organic chemistry and networking opportunities will be offered to further manifest the students' interest in a career in chemistry. Graduate and undergraduate students involved in this program will be trained at the interface of chemistry and biology. They will obtain skills to perform (in)organic syntheses including polymerizations, conduct spectroscopic and calorimetric characterization of coordination events, and determine kinetic profiles of enzymes and synthetic catalysts. Additionally, they will participate in outreach programs to the general public with particular focus on the African-American students in rural Alabama.