D. Bromme et al., NOVEL N-PEPTIDYL-O-ACYL HYDROXAMATES - SELECTIVE INHIBITORS OF CYSTEINE PROTEINASES, Biochimica et biophysica acta, 1202(2), 1993, pp. 271-276
A series of N-peptidyl-O-acyl hydroxamates with a lysine in P1 was syn
thesized and tested as inactivators of lysosomal cysteine proteinases
(cathepsins S, L, B and H) and trypsin-like serine proteinases (trypsi
n, thrombin, plasmin, t-PA). N-peptidyl-O-acyl hydroxamates were shown
to be selective inhibitors of cysteine proteinases. With the exceptio
n of cathepsin H, the lysosomal cysteine proteinases were inactivated
2-5 orders of magnitude more rapidly than serine proteinases with a co
mparable primary substrate specificity. The highest second-order rate
constants of inactivation for the cysteine proteinases are in the rang
e of 10(5)-10(6) M-1 s-1. The order of inhibitor specificity for the c
ysteine proteinases is comparable to the enzyme's substrate specificit
y.