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
1
Department of Bioorganic Chemistry, Wrocław University of Science and Technology, Wybrzeże Wyspiańskiego 27, 50-370 Wrocław, Poland
2
Faculty of Chemistry, University of Opole, ul. Oleska 48, 45-052 Opole, Poland
*
Author to whom correspondence should be addressed.
Pharmaceuticals 2019, 12(3), 139; https://doi.org/10.3390/ph12030139
Received: 9 August 2019 / Revised: 13 September 2019 / Accepted: 16 September 2019 / Published: 17 September 2019
(This article belongs to the Special Issue Design of Enzyme Inhibitors as Potential Drugs)
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.
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Keywords:
aminopeptidases; inhibitors; aminophosphonate; phenylglycine analogues; fluorine substituted; molecular modeling
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MDPI and ACS Style
Wanat, W.; Talma, M.; Pawełczak, M.; Kafarski, P. 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. Pharmaceuticals 2019, 12, 139.
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