Phosphonic Acid Analogs of Fluorophenylalanines as Inhibitors of Human and Porcine Aminopeptidases N: Validation of the Importance of the Substitution of the Aromatic Ring
A library of phosphonic acid analogs of phenylalanine substituted with fluorine, chlorine and trifluoromethyl moieties on the aromatic ring was synthesized and evaluated for inhibitory activity against human (hAPN) and porcine (pAPN) aminopeptidases. Fluorogenic screening indicated that these analog...
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| Format: | Article |
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MDPI AG
2020-04-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/10/4/579 |
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| author | Weronika Wanat Michał Talma Błażej Dziuk Jean-Luc Pirat Paweł Kafarski |
| author_facet | Weronika Wanat Michał Talma Błażej Dziuk Jean-Luc Pirat Paweł Kafarski |
| author_sort | Weronika Wanat |
| collection | DOAJ |
| description | A library of phosphonic acid analogs of phenylalanine substituted with fluorine, chlorine and trifluoromethyl moieties on the aromatic ring was synthesized and evaluated for inhibitory activity against human (hAPN) and porcine (pAPN) aminopeptidases. Fluorogenic screening indicated that these analogs are micromolar or submicromolar inhibitors, both enzymes being more active against hAPN. In order to better understand the mode of the action of the most active compounds, molecular modeling was used. It confirmed that aminophosphonic portion of the enzyme is bound nearly identically in the case of all the studied compounds, whereas the difference in activity results from the placement of aromatic side chain of an inhibitor. Interestingly, both enantiomers of the individual compounds are usually bound quite similarly. |
| first_indexed | 2024-03-10T20:33:51Z |
| format | Article |
| id | doaj.art-596fb92edd8d4c5193dbc1cb2052a47a |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T20:33:51Z |
| publishDate | 2020-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-596fb92edd8d4c5193dbc1cb2052a47a2023-11-19T21:10:11ZengMDPI AGBiomolecules2218-273X2020-04-0110457910.3390/biom10040579Phosphonic Acid Analogs of Fluorophenylalanines as Inhibitors of Human and Porcine Aminopeptidases N: Validation of the Importance of the Substitution of the Aromatic RingWeronika Wanat0Michał Talma1Błażej Dziuk2Jean-Luc Pirat3Paweł Kafarski4Department of Bioorganic Chemistry, Wroclaw University of Science and Technology, Wybrzeże Wyspiańskiego 27, 50-370 Wrocław, PolandDepartment of Bioorganic Chemistry, Wroclaw University of Science and Technology, Wybrzeże Wyspiańskiego 27, 50-370 Wrocław, PolandDepartment of Bioorganic Chemistry, Wroclaw University of Science and Technology, Wybrzeże Wyspiańskiego 27, 50-370 Wrocław, PolandICGM, University of Montpellier, ENSCM, CNRS, 34296 Montpellier, FranceDepartment of Bioorganic Chemistry, Wroclaw University of Science and Technology, Wybrzeże Wyspiańskiego 27, 50-370 Wrocław, PolandA library of phosphonic acid analogs of phenylalanine substituted with fluorine, chlorine and trifluoromethyl moieties on the aromatic ring was synthesized and evaluated for inhibitory activity against human (hAPN) and porcine (pAPN) aminopeptidases. Fluorogenic screening indicated that these analogs are micromolar or submicromolar inhibitors, both enzymes being more active against hAPN. In order to better understand the mode of the action of the most active compounds, molecular modeling was used. It confirmed that aminophosphonic portion of the enzyme is bound nearly identically in the case of all the studied compounds, whereas the difference in activity results from the placement of aromatic side chain of an inhibitor. Interestingly, both enantiomers of the individual compounds are usually bound quite similarly.https://www.mdpi.com/2218-273X/10/4/579phosphonic acid analogshuman and porcine aminopeptidasemolecular modelingfluorineinhibitors |
| spellingShingle | Weronika Wanat Michał Talma Błażej Dziuk Jean-Luc Pirat Paweł Kafarski Phosphonic Acid Analogs of Fluorophenylalanines as Inhibitors of Human and Porcine Aminopeptidases N: Validation of the Importance of the Substitution of the Aromatic Ring Biomolecules phosphonic acid analogs human and porcine aminopeptidase molecular modeling fluorine inhibitors |
| title | Phosphonic Acid Analogs of Fluorophenylalanines as Inhibitors of Human and Porcine Aminopeptidases N: Validation of the Importance of the Substitution of the Aromatic Ring |
| title_full | Phosphonic Acid Analogs of Fluorophenylalanines as Inhibitors of Human and Porcine Aminopeptidases N: Validation of the Importance of the Substitution of the Aromatic Ring |
| title_fullStr | Phosphonic Acid Analogs of Fluorophenylalanines as Inhibitors of Human and Porcine Aminopeptidases N: Validation of the Importance of the Substitution of the Aromatic Ring |
| title_full_unstemmed | Phosphonic Acid Analogs of Fluorophenylalanines as Inhibitors of Human and Porcine Aminopeptidases N: Validation of the Importance of the Substitution of the Aromatic Ring |
| title_short | Phosphonic Acid Analogs of Fluorophenylalanines as Inhibitors of Human and Porcine Aminopeptidases N: Validation of the Importance of the Substitution of the Aromatic Ring |
| title_sort | phosphonic acid analogs of fluorophenylalanines as inhibitors of human and porcine aminopeptidases n validation of the importance of the substitution of the aromatic ring |
| topic | phosphonic acid analogs human and porcine aminopeptidase molecular modeling fluorine inhibitors |
| url | https://www.mdpi.com/2218-273X/10/4/579 |
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