Single Conformation Spectroscopy and Isomerization Dynamics of Synthetic Foldamers

在这个由化学系实验物理化学项目资助的奖项中，普渡大学的Timothy Zwier教授及其研究生和本科生将研究一系列β-肽，γ-肽和杂合物（例如，α/β）含有2-10个残基的合成折叠体。这些分子将被研究，无论是孤立的中性分子在超音速膨胀冷却或离子冷却到10 K的低温冷却离子阱。重点将放在与天然存在的α-肽不同的分子上，这些分子具有一个（β）或两个（γ）额外的碳原子将酰胺基团分开，使它们具有额外的灵活性，并开辟了更广泛的二级结构，这些二级结构可以模仿或改进自然界中发现的二级结构。Zwier教授和他的团队将使用基于激光的方法，使他们能够记录单一构象的红外和紫外光谱，而不受彼此干扰，并确定它们的相对种群。这些结果也将为蛋白质和合成折叠体行为的计算机模型的准确性提供基准测试。最后，激光将被用来启动构象异构化，以确定能量，时间尺度，和能量流与异构化过程。该研究项目将通过对这些合成折叠体的固有结构偏好提供基本见解来影响整个社会，这些合成折叠体正被合成化学家应用于广泛的生物医学和药物发现应用。威斯康星大学麦迪逊分校的Sam Gellman和他的团队正在合作进行这项研究，合成测试其行为特定方面的折叠分子。设计独特的螺旋支架，定制与特定的生物受体的相互作用，需要的知识，并控制，个别亚单位的结构偏好，它们是由。与foldamer领域领先的合成团队的密切合作确保了紧密耦合的反馈，这将最大限度地提高该项目结果对生物医学应用的益处。

In this award, funded by the Experimental Physical Chemistry Program of the Division of Chemistry, Professor Timothy Zwier of Purdue University and his graduate and undergraduate students will investigate the spectroscopy and isomerization dynamics of a series of beta-peptide, gamma-peptide, and hybrid (e.g., alpha/beta) synthetic foldamers containing 2-10 residues. These molecules will be studied either as isolated neutral molecules cooled in a supersonic expansion or as ions cooled to 10 K in a cryo-cooled ion trap. The focus will be on molecules that differ from naturally-occurring alpha-peptides in having one (beta) or two (gamma) extra carbon atoms separating the amide groups, giving them additional flexibility and opening up a wider range of secondary structures that either mimic or improve on those found in nature. Professor Zwier and his team will use laser-based methods that enable them to record infrared and ultraviolet spectra of single conformations free from interference from one another, and to determine their relative populations. The results will also provide benchmark tests of the accuracy of computer models of the behavior of proteins and synthetic foldamers. Finally, lasers will be used to initiate conformational isomerization in order to determine the energies, time-scales, and energy flow associated with the isomerization process. This research project will impact society at large by providing fundamental insight to the inherent structural preferences of these synthetic foldamers, which are being applied by synthetic chemists to a wide range of biomedical and drug-discovery applications. Sam Gellman and his group at University of Wisconsin-Madison are collaborating in this study, synthesizing foldamers that test particular aspects of their behavior. The design of unique helical scaffolds tailor-made to interact with specific biological receptors requires a knowledge of, and control over, the structural preferences of the individual sub-units of which they are made. The strong collaboration with a leading synthetic group in the foldamer field ensures close-coupled feedback that will maximize the benefit of this project's results towards biomedical applications.