Molecular Templates for Creating Artificial Protein Structures

有机和大分子化学计划通过这一更新奖支持加州大学欧文分校化学系詹姆斯·s·诺威克博士的工作。该研究旨在通过以下方式扩展人工蛋白质结构的早期工作：1)制备更大的低聚脲支架，将四条或四条以上的肽链结合在一起，形成b-sheet； 2)在链中加入更长的肽（五肽和七肽）；3)创建更大的b-sheet结构；4)结合发夹成核剂，允许反平行的b-sheet形成；5)使用一种新型模板，将两个b-sheet定位在面对面的方向，创建b-sheet三明治。这项工作还将开发改进的分子建模参数，并将b-sheet结构的形成从氯仿扩展到水溶液。拟议的研究包括设计和合成通过使用分子支架将肽（连接氨基酸的短序列）连接到受控结构中形成的蛋白质模拟物。它将提高我们对蛋白质折叠方式的理解，并可能导致合成新材料和能够进行所需反应的人工酶。参与这项工作的学生将发展蛋白质合成和表征领域的技能，并将学习如何以合乎逻辑的、逐步的方式开发化学系统。

With this renewal award the Organic and Macromolecular Chemistry Program supports the work of Dr. James S. Nowick of the Department of Chemistry of the University of California at Irvine. The research aims to extend earlier work on artificial protein structures by: 1) preparing larger oligourea scaffolds that hold four or more peptide strands together and cause b-sheet formation, 2) including longer (penta- and hepta-) peptides in the strands, 3) creating larger b-sheet structures, 4) incorporating hairpin nucleators that will permit antiparallel sheet formation, and 5) creating b-sheet sandwiches using a new type of template that will position two b-sheets in a face-to-face orientation. The work will also develop improved molecular modeling parameters, and extend b-sheet structure formation from chloroform to water solutions.The proposed research involves the design and synthesis of protein mimics formed by joining peptides (short sequences of linked aminoacids) into controlled structures by the use of molecular scaffolds. It will improve our understanding of how proteins fold, and could lead to the synthesis of new materials and artificial enzymes capable of carrying out desired reactions. The students involved in the work will develop skills in the areas of protein synthesis and characterization, and will learn how to develop chemical systems in a logical, stepwise manner.