RUI: Nucleating Peptide Secondary Structures via Metal-Alkyne Coordination

Trinity University化学系的Timothy Curran博士得到了化学系无机、生物无机和有机化学项目的支持，以探索使用钨和钼的双炔络合物作为支架，将肽组装成定义的构象。第一个目标是制备含有附加炔基的小肽。这些将被设计成使得炔部分与钼或钨中心的配位将产生双炔复合物，其中肽被限制在特定构象中。靶标将包括具有适于形成β-转角、β-折叠（平行和反平行）和α-螺旋的炔的肽。将评价这些肽形成钨或钼双炔络合物的能力，并使用NMR光谱法测定金属络合物中肽的构象。我们的目标是开发一个简单的，合理的方法来产生小肽与确定的构象。这个RUI项目涉及大量的本科生参与。 肽和蛋白质的物理和生化性质由它们在溶液中的形状决定。确定蛋白质特定部分的结构和活性之间关系的一个简单方法是只合成蛋白质的这一部分并分析其行为。不幸的是，小肽通常不呈现确定的构象;相反，它们呈现各种各样的构象。这项研究将试图通过将肽连接到金属中心来克服这个问题，以这种方式迫使肽进入一个定义的，特定的构象。这一发展将促进从头蛋白质的设计，并允许在蛋白质化学中的结构和活性之间的关系的评估。除了科学贡献，这项工作将为本科生提供优秀的研究培训，使他们在有机合成，有机金属合成和NMR光谱学方面的经验。

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.