title: Unusual activity pattern of leucine aminopeptidase inhibitors based on phosphorus containing derivatives of methionine and norleucine.
abstract: 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.
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, V.V.I., Flemingovo Nám., Praha, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Pícha
authors.forename: Radek
authors.initials: R
authors.lastname: Liboska
authors.forename: Miloš
authors.initials: M
authors.lastname: Buděšínský
authors.forename: Jiři
authors.initials: J
authors.lastname: Jiráček
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Pawełczak
authors.forename: Artur
authors.initials: A
authors.lastname: Mucha
mesh_terms: D000818:Animals; D004789:Enzyme Activation / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007668:Kidney / Q000201:enzymology; D007931:Leucyl Aminopeptidase / Q000037:antagonists & inhibitors*; D008715:Methionine / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D009646:Norleucine / Q000737:chemistry / Q000494:pharmacology; D010758:Phosphorus / Q000737:chemistry*; D013552:Swine
chemical_list: D004791:Enzyme Inhibitors; D010758:Phosphorus; D009646:Norleucine; D008715:Methionine; D007931:Leucyl Aminopeptidase