Molecular Templates for Creating Artificial Protein Structures

通过这个续展奖项，有机和高分子化学项目支持加州大学欧文分校化学系的詹姆斯·S·诺维克博士的工作。这项研究旨在通过以下方式扩展人造蛋白质结构的早期工作：1)制备将四个或更多肽链结合在一起并导致b-折叠形成的更大的寡脲支架，2)在链中包含更长的(五和七)肽，3)创建更大的b-折叠结构，4)加入允许反平行折叠的发夹核仁，以及5)使用一种新型模板创建b-折叠三明治，该模板将以面对面的方向定位两个b-折叠。这项工作还将开发改进的分子建模参数，并将b-折叠结构的形成从氯仿扩展到水溶液。拟议的研究涉及通过使用分子支架将多肽(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的设计和合成。它将提高我们对蛋白质如何折叠的理解，并可能导致新材料和能够进行所需反应的人造酶的合成。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，并将学习如何以逻辑、循序渐进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.