NONCONVENTIONAL ENZYME CATALYSIS - APPLICATION OF PROTEASES AND ZYMOGENS IN BIOTRANSFORMATIONS

One of the attractions of using enzymes for chemical syntheses is the control of stereochemistry: problems of racemization that attend chemi cal C-N ligation methods are completely avoided, Furthermore, the enzy matic approach has the advantage that only minimal protection-deprotec tion steps are involved, The impetus to develop non-conventional catal ysis procedures has sprung from the lack of usable native enzymes that normally catalyze the formation of peptide bonds for biotransformatio n, In peptide syntheses that make use of the 'reverse hydrolysis poten tial' of proteases several problems need to be considered, especially the necessity of minimizing competing hydrolysis of weakly activated a cyl donor esters and the need to circumvent undesired product cleavage , Some approaches to suppress competitive reactions have been develope d in our group, namely leaving group manipulations at the acyl donor i n kinetically controlled reactions, enzymatic synthesis in organic sol vent-free micro-aqueous systems, cryoenzymatic peptide synthesis, and biotransformations in frozen aqueous systems, Finally, for the first t ime, zymogens, which are known as catalytically inactive precursors of proteases, could be used as biocatalysts for practically irreversible peptide bond formation.