The focus of this research is the development of generally applicable, reliable and rapid procedures for the chemical synthesis of longer peptides and small proteins (range of incorporated amino acids 75-100 or higher). Parallel studies of the segment condensations and stepwise approaches will be undertaken with a view to eventual elaboration of the latter technique to allow the quick synthesis of products of high purity without the need for elaborate purification. Promising new coupling techniques based on FMOC amino acid fluorides and 1-hydroxy-7-azobenzotriazole (HOAt) will be emphasized. Because of neighboring group effects, the latter offers the opportunity of coupling both urethane-protected amino acids and peptide segments wthout racemization. Stable FMOC-protected amino acid fluoride derivatives will be made for histidine and arginine. When the full range of acid fluorides is available, model syntheses of 29-, 41- and 76-amino acid peptides will be examined as tests of the new methodolgy. The same models will be assembled via HOAt-derived reagents using both stepwise and segment coupling protocols. %%% With this award, the Synthetic Organic Program is supporting the research of Dr. Louis A. Carpino of the Department of Chemistry at the University of Massachusetts Amherst. Professor Carpino will focus his work on the development of generally applicable, reliable and rapid procedures for the chemical synthesis of longer peptides and small proteins. Parallel studies of the segment condensation and stepwise approaches will be undertaken with the view to eventual elaboration of the latter technique to allow the rapid synthesis of products of high purity without the need for tedious purification. Quick, reliable methods for the chemical synthesis of higher peptides are needed in connection with the increasing use of such substances in the fields of medicinal chemistry, drug discovery and material science.
