6533b836fe1ef96bd12a14e2

RESEARCH PRODUCT

Phosphonic Acid Analogues of Phenylglycine as Inhibitors of Aminopeptidases: Comparison of Porcine Aminopeptidase N, Bovine Leucine Aminopeptidase, Tomato Acidic Leucine Aminopeptidase and Aminopeptidase from Barley Seeds

Paweł KafarskiMichał TalmaMałgorzata PawełczakWeronika Wanat

subject

aminophosphonateMolecular modelStereochemistryPharmaceutical Sciencelcsh:Medicinelcsh:RS1-441AminopeptidaseArticlelcsh:Pharmacy and materia medica03 medical and health sciences0302 clinical medicineDrug Discoveryinhibitorsaminopeptidases030304 developmental biologychemistry.chemical_classification0303 health sciencesChemistrymolecular modelingAminopeptidase Nlcsh:RAromaticityAffinitiesEnzymefluorine substitutedAminophosphonate030220 oncology & carcinogenesisMolecular Medicinephenylglycine analoguesLeucine

description

The inhibitory activity of 14 racemic phosphonic acid analogs of phenylglycine, substituted in aromatic rings, towards porcine aminopeptidase N (pAPN) and barley seed aminopeptidase was determined experimentally. The obtained patterns of the inhibitory activity against the two enzymes were similar. The obtained data served as a basis for studying the binding modes of these inhibitors by pAPN using molecular modeling. It was found that their aminophosphonate fragments were bound in a highly uniform manner and that the difference in their affinities most likely resulted from the mode of substitution of their phenyl rings. The obtained binding modes towards pAPN were compared, with these predicted for bovine lens leucine aminopeptidase (blLAP) and tomato acidic leucine aminopeptidase (tLAPA). The performed studies indicated that the binding manner of the phenylglycine analogs to biLAP and tLAPA are significantly similar and differ slightly from that predicted for pAPN.

yearjournalcountryeditionlanguage
2019-09-17Pharmaceuticals
10.3390/ph12030139https://doi.org/10.3390/ph12030139