Synthetic Helizyme Enzymes
Final technical rept.
COLORADO UNIV HEALTH SCIENCES CENTER DENVER
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Work on this contract consisted of further studies on design, synthesis and catalytic activities of our synthetic chymohelizyme CHZ molecules. CHZs consist of a bundle of four amphipathic alpha-helices joined covalently at their carboxy-terminus and bearing on their amino ends the amino acids that constitute the active site of chymotrypsin ChTr. The first of these molecules, CHZ-1, demonstrated ChTr-like catalysis of hydrolysis of ChTr substrates. Design studies, using molecular graphics computer software, were directed toward improving the stability of the active site. Synthesis studies were directed toward improving the synthetic methods used. Extensive studies were carried out on improving solid phase peptide synthesis resins and protecting groups for this demanding synthesis. Studies of catalysis characterized the parameters of hydrolysis of nitrophenyl esters by CHZ-1 and several analogs. Rate of hydrolysis of acylamino acid esters catalyzed by chymohelizymes depends on the nature of the acyl group, the nature of the amino acid, and the nature of the ester group. Enzymes, Synthetic, Chymohelizyme, Solid phase peptide synthesis.