Parasite proteinases and amino acid metabolism: possibilities for chemotherapeutic exploitation

Abstract

Parasite enzymes involved in proteolysis and amino acid metabolism have attracted considerable attention over the last decade. Nevertheless, current knowledge is extensive for just a few parasites and several enzymes. Most enzymes remain largely unexplored. This review concentrates upon a selection of the better studied enzymes and the potentially valuable approaches now being adopted in their study. We present a personal view on the most suitable strategies for exploiting this area of parasite biochemistry with novel antiparasite drugs. The content of the review reflects our own work and interests, but we have aimed to include a sufficiently broad range of topics so that this overview serves as a useful introduction for those new to the subject.There have been several reviews that provide good coverage of the appropriate literature (Barrett, 1991; McKerrow et al. 1993; North & Lockwood, 1995; Sakanari et al. 1995; Robertson et al. 1996; Vial, 1996; Coombs & Mottram, 1997; Walker & Barrett, 1997), therefore we detail here just some of the publications and refer readers to the reviews quoted for further information. This treatise mainly highlights progress made in studies with parasitic protozoa. Parasitic worms present more difficult problems for drug designers and there has been only limited progress to date in this area of biochemistry; we include here mention of just some of the more exciting advances so far.