Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, V.V.I., Flemingovo Nám., Praha, Czech Republic.
J Enzyme Inhib Med Chem. 2011 Apr;26(2):155-61. doi: 10.3109/14756366.2010.482047. Epub 2010 Jun 28.
Ligands containing bulky aliphatic P1 residues exhibit a high affinity towards cytosolic leucine aminopeptidase, a bizinc protease of biomedical significance. According to this specificity, a series of phosphonic and phosphinic compounds have been put forward as novel putative inhibitors of the enzyme. These phosphonic and phosphinic compounds were derivatives of methionine and norleucine as both single amino acids and dipeptides. The designed inhibitors were synthesised and tested towards the peptidase isolated from porcine kidneys using an improved separation procedure affording superior homogeneity. Unexpectedly, organophosphorus derivatives of methionine and norleucine exhibited moderate activity with K(i) values in the micromolar range.
配体含有大体积脂肪族 P1 残基，对具有生物医学意义的胞质亮氨酸氨肽酶（一种双锌蛋白酶）表现出高亲和力。根据这种特异性，已经提出了一系列膦酸和亚膦酸化合物作为该酶的新型潜在抑制剂。这些膦酸和亚膦酸化合物是蛋氨酸和正亮氨酸的衍生物，包括单个氨基酸和二肽。使用改进的分离程序合成并测试了设计的抑制剂，该程序可提供更高的均一性。出乎意料的是，蛋氨酸和正亮氨酸的有机磷衍生物表现出中等活性，其 K(i) 值在微摩尔范围内。
