STUDIES ON BETA-AMINOACID OLIGOMERS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 我们小组参与非天然聚合物系统的设计和研究，主要是β-氨基酸低聚物。这些分子是令人感兴趣的，因为它们模仿天然肽和蛋白质，因为它们具有明确的折叠模式。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。非天然肽系统具有作为药物的潜在用途（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是必要的，它们的合理设计和解释其生物学特性。 我们小组先前的工作已经很好地利用了高场NMR来阐明几种β-氨基酸寡聚物的结构（J. Am. 2000，122，4821-4822）。该研究调查了用基于吡咯烷的残基取代基于环戊基的β-氨基酸残基的结构效应。本文研究了非环状残基对齐聚物结构的影响。与以前在类似系统上的工作一样，由于500和600 MHz光谱仪的良好分散性和强远程ROE的观察，非水溶液（CD 3OH）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长程ROE较弱而变得复杂。这是水溶液中结构较少的结果。我们相信，与类似分子的情况一样，750 MHz NMR的灵敏度增强将有助于信号的分辨率和更长距离ROE的检测。

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.