6533b7d9fe1ef96bd126c3ac
RESEARCH PRODUCT
Unusual activity pattern of leucine aminopeptidase inhibitors based on phosphorus containing derivatives of methionine and norleucine
Jiří JiráčekMiloš BuděšínskýArthur MuchaJan PíchaRadek LiboskaMałgorzata Pawełczaksubject
aminophosphinatesaminophosphonatesSwineStereochemistrymedicine.medical_treatmentNorleucinenorleucineKidneyAminopeptidaseLeucyl Aminopeptidasechemistry.chemical_compoundinhibitorsDrug DiscoverymedicineAnimalsEnzyme Inhibitorscytosolic leucine aminopeptidasemethioninePharmacologychemistry.chemical_classificationProteaseMethionineMolecular StructurePhosphorusphosphorus containing dipeptidesGeneral MedicineAmino acidEnzyme ActivationCytosolEnzymechemistryBiochemistryLeucinedescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2010-06-28 | Journal of Enzyme Inhibition and Medicinal Chemistry |