STUDIES ON BETA-AMINOACID OLIGOMERS

β-氨基酸低聚物的研究

• 批准号: 7598802
• 负责人: SAMUEL H. GELLMAN
• 金额: $ 0.04万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-01 至 2008-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7598802
• 关键词: Amino Acids; Biological; Computer Retrieval of Information on Scientific Projects Database; Detection; Funding; Grant; Institution; Pattern; Peptides; Pharmaceutical Preparations; Polymers; Property; Proteins; Range; Research; Research Design; Research Personnel; Resolution; Resources; Signal Transduction; Solutions; Source; Structure; System; United States National Institutes of Health; Work; antimicrobial drug; aqueous; base; catalyst; design; interest; scaffold

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Our group is involved in the design and study of unnatural polymeric systems, principally beta-amino acid oligomers. These molecules are of interest because they mimic natural peptides and proteins in that they have well defined folding patterns. The actual structures that they form as well as the stability of these folded forms differ dramatically from natural systems. Unnatural peptide systems have potential uses as drugs (we are presently investigating polycationic beta-amino acid antimicrobial agents) as well as structural scaffolds for catalyst design and other polymer aplications. Structural information about these oligomers is necessary for their rational design and the interprestation of their biological properties. Previous work in our group has made good use of high field NMR to elucidate the structure of several beta-amino acid oligomers (J. Am. Chem. Soc. 2000, 122, 4821-4822 ). That study investigated the structural effects of making substitutions of cyclopentyl based beta-amino acid residues by pyrolidine based residues. The present study is investigating the effects of acyclic residues on oligomer structure. As with the previous work on similar systems, structure elucidation in non-aqueous solution (CD3OH) has proved to be straight forward due to good dispersion and observation of strong long range ROEs of 500 and 600 MHz spectrometers. Structural studies in aqueous solution are complicated by poor dispersion and weaker long range ROEs. This is a consequence of there being less structure in aqueous solution. We believe, as was the case in similar molecules, that the enhanced sensitivity of the 750MHz NMR will aid in the resolution of signals and in the detection of more long-range ROEs.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 我们团队致力于非天然聚合物体系的设计和研究，主要是β-氨基酸低聚物。这些分子之所以令人感兴趣，是因为它们模仿天然的多肽和蛋白质，因为它们有明确的折叠模式。它们形成的实际结构以及这些折叠形式的稳定性与自然系统截然不同。非天然多肽系统具有潜在的药物用途(我们目前正在研究聚阳离子β-氨基酸抗菌剂)，以及用于催化剂设计和其他聚合物应用的结构支架。这些低聚物的结构信息对于它们的合理设计和生物学特性的解释是必要的。我们小组以前的工作很好地利用了高场核磁共振来阐明几个β-氨基酸低聚物的结构(J.Am化学。SoC。2000、122、4821-4822)。这项研究调查了以吡咯烷为基础的残基取代环戊基的β-氨基酸残基的结构效应。本研究旨在探讨无环残基对齐聚物结构的影响。与以前在类似体系中的工作一样，由于良好的分散性和在500和600 MHz光谱仪上观察到的强大的远程ROE，在非水溶液(CD3OH)中的结构解析已被证明是直接的。水溶液中的结构研究由于分散性差和较弱的长程ROE而变得复杂。这是水溶液中结构较少的结果。我们相信，就像在类似分子中的情况一样，750 MHz核磁共振的增强灵敏度将有助于信号的分辨率和更远距离ROE的检测。