Collaborative Research: Intrinsic Gas-phase Properties of Amino Acids and Peptides: Thermochemistry, Fragmentation Mechanisms, H/D exchange and IRMPD Spectroscopy.

通过这一奖项，化学结构、动力学和机制计划支持威廉与玛丽学院的John C.Poutsma教授和Old Dominion大学的Jennifer Poutsma教授的合作研究。John Poutsma教授利用基于质谱学的实验来研究氨基酸的结构和它们的气相能量特性之间的微妙相互作用。他正在研究一类被称为非蛋白生成氨基酸(NPAA)的化合物，这种化合物天然存在于植物和真菌中，但不用于蛋白质合成。许多NPAA对人类和其他动物有毒，部分原因是结构上与20种常见蛋白质氨基酸(PAA)中的一种或多种相似。NPAA可以通过多种生物途径与PAAS竞争，包括被误结合到蛋白质和多肽中。这些实验将进一步了解NPAA作为独立实体以及在结合到小肽中时的内在化学。Jennifer Poutsma教授正在进行密度泛函理论计算，以支持和指导实验研究。这两个研究项目都通过本科生研究人员的培训将研究和教育部分整合在一起。这项提案中概述的绝大多数研究项目都是由威廉、玛丽和老多米尼恩大学的本科生进行的。进行独立研究有助于这些学生在先进计算化学的支持下，接触到与生物相关的机械质谱学的现代研究。在这项研究中，双肽的本征气相热化学性质正在使用三重四极杆仪器中的扩展动力学方法进行测定。具体地说，PI正在研究含有Pro或其非蛋白质氨基酸类似物氮杂环丁酸-2-羧酸或吡哌酸的二肽的气相酸碱化学。绝对气相热化学性质将在TSQ量子三四极仪器中使用扩展动力学方法(EKM)来确定。合作研究小组正致力于确定环大小和构象灵活性对这些物种的酸碱性质的影响，目的是应用这些知识来更好地理解含脯氨酸的多肽的低能串联质谱学实验中选择性碎裂的机制。含有这些4-环和6-环类似物的脯氨酸是一种典型的β转角形成氨基酸，在化学生物学和肽设计界引起了极大的兴趣。这些研究的结果可能会引起这些社区的科学家的兴趣。

With this award, the Chemical Structure, Dynamics and Mechanisms program is supporting the collaborative research of Professor John C. Poutsma at the College of William and Mary and Professor Jennifer Poutsma at Old Dominion University. Professor John Poutsma employs mass spectrometry-based experiments to study the subtle interplay between the structure of amino acids and their gas-phase energetic properties. He is studying a class of compounds known as non-proteinogenic amino acids (NPAA), which are found naturally in plants and fungi, but are not used in protein synthesis. Many NPAAs are toxic to humans and other animals in part due to structural similarity to one or more of the twenty common protein amino acids (PAA). NPAAs can compete with PAAs in a variety of biological pathways including being mis-incorporated into proteins and peptides. These experiments will further understanding of the intrinsic chemistry of NPAAs as isolated entities and when incorporated into small peptides. Professor Jennifer Poutsma is performing density functional theory calculations that support and guide the experimental studies. Both research programs integrate research and educational components through the training of undergraduate researchers. The vast majority of the research projects outlined in this proposal are being performed by undergraduates at William and Mary and Old Dominion University. Performing independent research helps expose these students to the modern research in biologically relevant, mechanistic mass spectrometry, supported by advanced computational chemistry.In this research, the intrinsic gas-phase thermochemical properties of di-peptides are being determined using the extended kinetic method in a triple quadrupole instrument. Specifically, the PIs are studying the gas-phase acid-base chemistry of dipeptides that contain proline or one of its non-protein amino acid analogs azetidine-2-carboxylic acid or pipecolic acid. Absolute gas-phase thermochemical properties will be determined using the extended kinetic method (EKM) in a TSQ Quantum triple-quadrupole instrument. The collaborative research team is working to determine the effects of ring-size and conformational flexibility on the acid-base properties of these species with the goal of applying this knowledge toward a better understanding the mechanisms for selective fragmentations in low-energy tandem mass spectrometry experiments of proline-containing peptides. Peptides containing these 4- and 6-ring analogues of proline, a typical beta-turn-forming amino acid are of considerable interest in chemical biology and peptide design circles. The results of these studies are likely to be of interest to scientists in these communities.