RUI: Nucleating Peptide Secondary Structures via Metal-Alkyne Coordination

点击翻译按钮获取中文摘要

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.