Demuth H U, Silberring J, Nyberg F
Department of Biotechnology, Martin-Luther-University of Halle, Saale, Germany.
J Enzyme Inhib. 1991;4(4):289-98. doi: 10.3109/14756369109030393.
N-peptidyl-O-acyl hydroxylamines have proven to be effective and selective mechanism-based inhibitors of serine and cysteine proteases as demonstrated using enzymes with specificities for hydrophobic amino acids at the cleavage site. Here, we report for the first time the inhibition of proteases able to accommodate cationic amino acid side chains in their binding pockets using compounds of this inhibitor class. Trypsin and papain are inactivated by enkephalin-analogue diacyl hydroxylamines in a time-dependent and irreversible manner exhibiting second-order rate constants in the range of 100-1000 M-1.s-1. In contrast, human cerebrospinal fluid dynorphin-converting enzyme (hCSFDCE) is inhibited only moderately by these inhibitors. Mechanistic implications have been derived.
N-肽基-O-酰基羟胺已被证明是基于机制的有效且选择性的丝氨酸和半胱氨酸蛋白酶抑制剂，这在使用对切割位点处疏水氨基酸具有特异性的酶时得到了证实。在此，我们首次报道了使用这类抑制剂化合物对能够在其结合口袋中容纳阳离子氨基酸侧链的蛋白酶的抑制作用。脑啡肽类似物二酰基羟胺以时间依赖性和不可逆的方式使胰蛋白酶和木瓜蛋白酶失活，其二级速率常数在100 - 1000 M⁻¹·s⁻¹范围内。相比之下，这些抑制剂对人脑脊液强啡肽转化酶（hCSFDCE）的抑制作用仅为中等程度。已得出相关机制方面的结论。
