The objectives of this research are twofold. First, we plan to continue with the development of the chemistry of solid phase peptide synthesis. This will include studies on the physical and chemical properties of the crosslinked polystyrene supports, the rates of mass transfer of reagents into the beads, the kinetics of the peptide-forming reactions, the elimination of several low-level side reactions, and the mechanism of strong, anhydrous aaid cleavage and deprotection reactions. Second, we plan to apply these synthetic techniques to the study of peptides and proteins of biological interest. Total and partial syntheses of such compounds and of selected analogs are designed to answer questions about mechanisms of action that are difficult to answer by studies on the naturally occurring peptides and proteins themselves. The target molecules include the enzymes ribonuclease and transcarboxylase, and immunoglobulin domain, a domain of plasminogen and the antibacterial peptides cecropin A, B and D.
