Abstract

The newly-discovered human aspartic proteinase, napsin A was not susceptible to protein inhibitors from potato, squash or yeast but was weakly inhibited by the 17 kDa polypeptide from Ascaris lumbricoides and potently by isovaleryl and lactoyl-pepstatins. A series of synthetic inhibitors was also investigated which contained in the P1-P1 positions the dipeptide analogue statine or its phenylalanine or cyclohexylalanine homologues and in which the residues occupying P4-P3 were varied systematically. On this basis, the active site of napsin A can be readily distinguished from other human aspartic proteinases.

Keywords: human aspartic proteinase, selectivity of inhibition, active site mapping, importance of s1/s3, hapsin a, napsin a inhibitor