RUI: Nucleating Peptide Secondary Structures via Metal-Alkyne Coordination

Timothy Curran博士，三一大学化学系，在化学系无机、生物无机和有机金属化学项目的支持下，探索使用钨和钼的双炔配合物作为支架，将肽组装成确定的构象。第一个目标是制备含有附加炔基的小肽。这些将被设计成使炔部分与钼或钨中心的配位将产生双炔配合物，其中肽被限制在特定的构象中。目标将包括具有适合形成-旋、-片（平行和反平行）和-螺旋的炔的肽。这些肽形成钨或钼双炔配合物的能力将被评估，金属配合物中的肽的构象将用核磁共振光谱方法确定。目标是开发一种简单，合理的方法来产生具有确定构象的小肽。这个RUI项目需要大量本科生的参与。多肽和蛋白质的物理和生化特性是由它们在溶液中的形状决定的。确定蛋白质特定部分的结构和活性之间关系的一种简单方法是只合成该部分蛋白质并分析其行为。不幸的是，小肽通常没有确定的构象；相反，它们具有各种各样的构象。本研究将寻求通过将肽连接到金属中心来克服这个问题，从而迫使肽形成一个明确的、特定的构象。这一发展将有助于设计新的蛋白质，并允许评估蛋白质化学中结构和活性之间的关系。除了科学贡献之外，这项工作将为本科生提供优秀的研究训练，使他们在有机合成，有机金属合成和核磁共振光谱方面获得经验。

Dr. Timothy Curran, Chemistry Department, Trinity University, is supported by the Inorganic, Bioinorganic, and Organometallic Chemistry Program of the Chemistry Division to explore the use of bis-alkyne complexes of tungsten and molybdenum as scaffolds for assembling peptides into defined conformations. The first goal is the preparation of small peptides that contain an appended alkyne group. These will be designed so that coordination of the alkyne moieties to a molybdenum or tungsten center will produce a bis-alkyne complex in which the peptide is constrained in a particular conformation. Targets will include peptides possessing alkynes suitable for formation of beta-turns, beta-sheets (parallel and antiparallel) and alpha-helices. The ability of these peptides to form tungsten or molybdenum bis-alkyne complexes will be evaluated and the conformation of the peptides in the metal complexes will be determined using NMR spectroscopic methods. The goal is to develop a simple, rational methodology for generating small peptides with defined conformations. This RUI project involves the heavy participation of undergraduate students. The physical and biochemical properties of peptides and proteins are determined by the shapes they adopt in solution. A simple way to determine the relationship between structure and activity for a particular section of a protein is to synthesize only that part of the protein and analyze its behavior. Unfortunately, small peptides generally do not assume defined conformations; rather, they assume a wide variety of conformations. This study will seek to overcome the problem by attaching the peptides to a metal center in such a way as to force the peptide into a defined, specific conformation. This development will facilitate the design of de novo proteins and allow the evaluation of relationships between structure and activity in protein chemistry. In addition to the scientific contributions, this work will provide undergraduate students with excellent training in research, giving them experience in organic synthesis, organometallic synthesis and NMR spectroscopy.