Lysis of trypanosomes by peptidyl fluoromethyl ketones

Peptidyl fluoromethyl ketones, improved reagents for inactivating cysteinyl and serine proteinases, have provided unexpected results when applied to intact trypanosomes. A lethal effect was observed but limited to the infectious phase of the parasitic growth cycle. Since the inhibitors are known only to act on proteases, the result implies the existence of a protease of critical importance during the infectious phase. A labelled inhibitor, Cbz-Ala-[3H]Phe-CH2F, indicated that the killing effect correlated with the labelling of a 68 kd protein in the trypomastigotes which we deduce is an essential protease.