NMR Spectroscopic Investigation of Peptide Aggregation

这个教师早期职业发展（Career）项目是在分析化学和表面化学的一般领域以及生物分析化学的子领域。在这项为期三年的持续资助期间，Larive教授和她在堪萨斯大学的学生将进行旨在提供肽一级结构，三维构象和聚集之间关系的详细理解的研究。这些研究将涉及五个具体目标，即(1)了解初级结构在聚集中的重要性；(2)进行肽构象分析；(3)测定肽扩散系数；(4)建立聚合模型；(5)通过考察不同溶剂、温度、pH值和离子强度条件下的聚集情况来检验模型。一个基于系统改变16个残基序列一级结构的合成肽家族将使用一套具有核磁共振（NMR）和圆二色性（CD）的实验技术进行研究。这些研究的结果应该表明氢键、偶极相互作用和疏水接触对这些肽聚集体稳定的相对贡献。在此资助期内，Larive教授将推行一项教育发展计划，其中包括重组和振兴本科分析化学实验室，为化学专业引入环境选项，以及增加本科生对研究的参与。肽和蛋白质聚集是一个根本性的和现实的重要问题。通过探索溶剂、pH值和离子强度等溶液条件的影响，该CAREER研究项目将为控制研究、治疗或商业目的表达的蛋白质聚集奠定实验结果的基础。这个CAREER项目的教育发展方面将丰富和拓宽堪萨斯大学的本科分析化学课程。

This Faculty Early Career Development (CAREER) project is in the general area of analytical and surface chemistry and in the subfield of bioanalytical chemistry. During the tenure of this three-year continuing grant, Professor Larive and her students at the University of Kansas will pursue research designed to provide a detailed understanding of the relationships between peptide primary structure, three-dimensional conformation, and aggregation. These studies will involve five specific aims, namely (1) to understand the importance of primary structure in aggregation; (2) to perform peptide conformation analysis; (3) to measure peptide diffusion coefficients; (4) to develop an aggregation model; and (5) to test the model by examining aggregation under various conditions of solvent, temperature, pH, and ionic strength. A family of synthetic peptides based on systematic alteration of primary structure of a sixteen-residue sequence will be examined using a suite of experimental techniques featuring nuclear magnetic resonance (NMR) and circular dichroism (CD). The results of these studies should indicate the relative contributions of hydrogen bonding, dipolar interactions, and hydrophobic contacts to the stabilization of aggregates of these peptides. Also during this grant period, Professor Larive will pursue an educational development plan that includes the reorganization and revitalization of the undergraduate analytical chemistry laboratory, introduction of an environmental option for chemistry majors, and increasing the involvement of undergraduates in research. Peptide and protein aggregation is a fundamentally and practically important problem. By exploring the effects of solution conditions such as solvent, pH, and ionic strength, this CAREER research project will produce a foundation of experimental results which will be useful in controlling aggregation of proteins expressed for research, therapeutic, or commercial purposes. The educational developmen t aspects of this CAREER project will enrich and broaden the undergraduate analytical chemistry curriculum at the University of Kansas.