Inhibition of hepatic protein degradation by synthetic analogues of chymostatin.

Analogues of the microbial proteinase inhibitor chymostatin have been synthesized. The two most promising analogues were tested on protein turnover in isolated rat hepatocytes. Their effect is much similar to the effect of chymostatin, but the analogues are even more powerful inhibitors, probably due to an increased effect on lysosomal thiol proteinases. The analogues blocked most of the lysosomal (i.e. methylamine-sensitive) degradation of endogenous protein and caused a 50% inhibition of the non-lysosomal degradation; the effect occurred rapidly and was reversed upon washing the cells. One of the analogues, Z-Arg-Leu-Phe(H), is the most potent inhibitor of hepatic protein degradation so far found.