Unusual activity pattern of leucine aminopeptidase inhibitors based on phosphorus containing derivatives of methionine and norleucine.

摘要: Ligands containing bulky aliphatic P1 residues exhibit a high affinity towards cytosolic leucine aminopeptidase, bizinc protease of biomedical significance. According to this specificity, series phosphonic and phosphinic compounds have been put forward as novel putative inhibitors the enzyme. These were derivatives methionine norleucine both single amino acids dipeptides. The designed synthesised tested peptidase isolated from porcine kidneys using an improved separation procedure affording superior homogeneity. Unexpectedly, organophosphorus exhibited moderate activity with Ki values in micromolar range.