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

0359040 - ÚOCHB 2012 RIV GB eng J - Journal Article
Pícha, Jan - Liboska, Radek - Buděšínský, Miloš - Jiráček, Jiří - Pawelczak, M. - Mucha, A.
Unusual activity pattern of leucine aminopeptidase inhibitors based on phosphorus containing derivatives of methionine and norleucine.
Journal of Enzyme Inhibition and Medicinal Chemistry. Roč. 26, č. 2 (2011), s. 155-161. ISSN 1475-6366. E-ISSN 1475-6374
R&D Projects: GA ČR GA203/06/1405; GA MŠMT(CZ) LC06077
Institutional research plan: CEZ:AV0Z40550506
Keywords : aminophosphonates * aminophospinates * methionine * norleucine * phosphorus containing dipeptides * cytosolic leucine aminopeptidase * inhibitors
Subject RIV: CC - Organic Chemistry
Impact factor: 1.617, year: 2011

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 Ki values in the micromolar range.
Permanent Link: http://hdl.handle.net/11104/0196914