New Peptidic Foldamer Structures

新的肽折叠体结构

• 批准号: 1565810
• 负责人: Samuel Gellman
• 金额: $ 53万
• 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: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2019-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1565810&HistoricalAwards=false
• 关键词: New; Peptidic; Foldamer; Structures

The Macromolecular, Supramolecular and Nanochemistry Program of the Chemistry Division supports the research of Professor Samuel Gellman, who is a faculty member in the Department of Chemistry at the University of Wisconsin - Madison. Gellman's group develops new types of protein-like molecules, based on biologically-inspired designs. Biological systems contain sequence-specific oligomers and polymers that fold to particular shapes. Gellman's laboratory creates unnatural oligomers, or "foldamers", that also adopt discrete shapes. This research employs beta- and gamma-amino acids as alternative building blocks to the natural alpha-amino acids. The protein folding process arranges key subunits into the precise three-dimensional arrays that are necessary for binding to other molecules and catalyzing chemical reactions. A central aim of the Gellman group's research is to develop synthetic foldamers that display protein-like binding and/or catalytic properties. These materials ultimately might surpass proteins in terms of specific functions. This basic research may lead to new types of drug molecules or new types of nanoscale manufacturing capabilities. Conducting this research provides outstanding interdisciplinary training to undergraduates and graduate students.The study of foldamers is an area of chemistry research that offers opportunities for invention in terms of basic research and practical development. This research focuses on cutting-edge challenges in terms of molecular design. One aim is to link understanding of small-molecule conformational propensities to the higher-order structure preferences that emerge in oligomers built from the smaller molecules. In particular, The Gellman group creates secondary structures containing beta- and/or gamma-amino acid residues that form new helical secondary structures with large internal cavities, a feature not found among protein secondary structures. A second aim is to leverage previously acquired knowledge of beta-peptide and alpha/beta-peptide folding behavior to arrange pairs of reactive groups in ways that catalyze synthetically useful reactions. A third aim focuses on quantitative assessment of structure-stability relationships for foldamer helices, information that has been largely unavailable to date. The research group seeks to understand how changes in subunit structure affects the stability of foldamer secondary structures. Progress toward each of these goals may improve understanding of relationships between molecular structure and function.

化学系的大分子、超分子和纳米化学项目支持威斯康星大学麦迪逊分校化学系教员塞缪尔·盖尔曼教授的研究。盖尔曼的团队在生物灵感设计的基础上开发了新型的类似蛋白质的分子。生物系统包含序列特异的低聚物和可折叠成特定形状的聚合物。盖尔曼的实验室制造了非天然的低聚物，或称“折叠体”，它们也具有不连续的形状。这项研究使用β-和伽马-氨基酸作为天然α-氨基酸的替代构件。蛋白质折叠过程将关键亚基排列成精确的三维阵列，这是与其他分子结合和催化化学反应所必需的。盖尔曼小组研究的一个中心目标是开发具有蛋白质样结合和/或催化特性的合成折叠体。就特定功能而言，这些材料最终可能会超过蛋白质。这项基础研究可能会带来新型药物分子或新型纳米级制造能力。进行这项研究为本科生和研究生提供了出色的跨学科培训。对折叠体的研究是化学研究的一个领域，在基础研究和实践开发方面提供了发明的机会。这项研究集中在分子设计方面的前沿挑战。一个目的是将对小分子构象倾向的理解与从小分子构建的低聚物中出现的高阶结构偏好联系起来。特别是，Gellman小组创建了包含β-和/或伽马-氨基酸残基的二级结构，这些结构形成了具有大内腔的新的螺旋二级结构，这是蛋白质二级结构中没有的特征。第二个目标是利用先前获得的关于β-肽和α/β-肽折叠行为的知识，以催化合成有用的反应的方式安排反应基团对。第三个目标侧重于定量评估折叠螺旋的结构-稳定性关系，这些信息到目前为止基本上是无法获得的。该研究小组试图了解亚基结构的变化如何影响折叠二级结构的稳定性。在这些目标中的每一个方面的进展可能会提高对分子结构和功能之间关系的理解。