New Peptidic Foldamer Structures

新的肽折叠体结构

• 批准号: 1307365
• 负责人: Samuel Gellman
• 金额: $ 45.6万
• 依托单位: University of Wisconsin-Madison
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2016-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1307365&HistoricalAwards=false
• 关键词: New; Peptidic; Foldamer; Structures

In this project funded by the Macromolecular, Supramolecular and Nanochemistry Program of the Chemistry Division, Professor Samuel Gellman of the University of Wisconsin at Madison will develop new oligomers with protein-like folding behavior ("foldamers"). This work will focus on the use of gamma-amino acid building blocks, to construct "gamma-peptides" that adopt novel shapes or for use in conjunction with alpha- and/or beta-amino acids to generate foldamers with more diverse backbones. The research is directed toward conformations that can ultimately be tailored to achieve specific molecular engineering goals. This experimental program includes three specific goals. One is to build upon the recent NSF-supported discovery of alpha / beta / gamma-peptides that mimic natural alpha-helices; an experimental strategy will be developed for quantifying the thermodynamics of alpha / beta / gamma-peptide folding, so that the subunits can be optimized. The second goal involves exploration of previously unknown types of gamma-amino acids as potential foldamer subunits. This effort will necessitate the development of new asymmetric synthesis methods. The third component of this program is directed toward unusual or unprecedented secondary structures (e.g., oval-shaped helices) that could ultimately be used to accomplish high-value tasks, such as mimicking expansive, information-rich surfaces on natural proteins. The broader impacts of this research will include training young scholars to be successful in highly intersciplinary and collaborative research environments, and the generation of tools can be used by many researchers to address molecular-level challenges in medicine, nanotechnology and other fields. Biological systems make heavy use of proteins to carry out complex tasks at the molecular level. Proteins are "oligomers": they are composed of multiple chemical subunits linked together in a long chain. The chain must fold into a specific, complex shape in order for the protein to become functional. This research project is part of a growing international effort, inspired by natural proteins, to create new types of synthetic oligomers that can adopt complex shapes and perform useful functions. Long-term outcomes of this basic research could include the development of new types of medicines, materials with unprecedented properties, and other useful chemical technologies.

在这项由化学系大分子、超分子和纳米化学计划资助的项目中，威斯康星大学麦迪逊分校的塞缪尔·盖尔曼教授将开发具有蛋白质样折叠行为的新低聚物(“折叠体”)。这项工作将集中在使用伽马-氨基酸构建块，以构建采用新形状或与α-和/或β-氨基酸一起使用以产生具有更多骨架的折叠蛋白的“伽马肽”。这项研究针对的是最终可以定制以实现特定分子工程目标的构象。这一实验计划包括三个具体目标。一个是建立在美国国家科学基金会支持的最近发现的模仿自然阿尔法螺旋的阿尔法/贝塔/伽马肽的基础上；将开发一种实验策略来量化阿尔法/贝塔/伽马肽折叠的热力学，以便对亚基进行优化。第二个目标涉及探索以前未知类型的伽马-氨基酸作为潜在的折叠分子亚单位。这就需要开发新的不对称合成方法。该计划的第三个组成部分是针对不寻常或史无前例的二级结构(例如，椭圆形螺旋)，这些二级结构最终可能被用来完成高价值的任务，例如模仿天然蛋白质上丰富的、可扩展的表面。这项研究的更广泛影响将包括培训年轻学者在高度跨学科和协作的研究环境中取得成功，许多研究人员可以使用这一代工具来应对医学、纳米技术和其他领域的分子层面的挑战。生物系统大量使用蛋白质在分子水平上执行复杂的任务。蛋白质是“低聚物”：它们由多个化学亚基组成，它们以长链连接在一起。链必须折叠成特定的、复杂的形状，才能使蛋白质具有功能。这项研究项目是受到天然蛋白质启发的日益增长的国际努力的一部分，目的是创造能够采用复杂形状和执行有用功能的新型合成低聚物。这项基础研究的长期成果可能包括开发新型药物、具有前所未有的性能的材料和其他有用的化学技术。