New Peptidic Foldamer Structures

在这个由化学学部大分子、超分子和纳米化学项目资助的项目中，威斯康星大学麦迪逊分校的Samuel Gellman教授将开发具有类似蛋白质折叠行为的新型低聚物（“折叠物”）。这项工作将侧重于使用γ -氨基酸构建块，构建采用新形状或与α -和/或β -氨基酸结合使用的“γ -肽”，以产生具有更多样化骨架的文件夹。这项研究的方向是最终可以定制的构象，以实现特定的分子工程目标。这个实验项目包括三个具体目标。一个是建立在最近由美国国家科学基金会支持的α / β / γ -肽的发现之上，这些肽模仿天然的α -螺旋；将开发一种实验策略来量化α / β / γ肽折叠的热力学，从而优化亚基。第二个目标涉及探索以前未知类型的γ -氨基酸作为潜在的折叠体亚基。这一努力将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前所未有的二级结构（例如，椭圆形螺旋），这些结构最终可用于完成高价值的任务，例如模拟天然蛋白质上膨胀的、信息丰富的表面。这项研究的更广泛的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，并且生成的工具可以被许多研究人员用来解决医学、纳米技术和其他领域的分子水平的挑战。生物系统在分子水平上大量使用蛋白质来完成复杂的任务。蛋白质是“低聚物”：它们由多个化学亚基连接在一起形成一条长链。蛋白质链必须折叠成特定的、复杂的形状才能发挥功能。受天然蛋白质的启发，国际上正在努力创造新型的合成低聚物，这些低聚物可以采用复杂的形状并具有有用的功能，该研究项目是其中的一部分。这项基础研究的长期成果可能包括开发新型药物、具有前所未有性能的材料和其他有用的化学技术。

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.