NMR and Docking Calculations Reveal Novel Atomistic Selectivity of a Synthetic High-Affinity Free Fatty Acid vs. Free Fatty Acids in Sudlow's Drug Binding Sites in Human Serum Albumin
- Publikationstyp:
- Zeitschriftenaufsatz
- Metadaten:
-
- Autoren
- Themistoklis Venianakis
- Alexandra Primikyri
- Till Opatz
- Stefan Petry
- Georgios Papamokos
- Ioannis P Gerothanassis
- Autoren-URL
- https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:001132296900001&DestLinkType=FullRecord&DestApp=WOS_CPL
- DOI
- 10.3390/molecules28247991
- eISSN
- 1420-3049
- Externe Identifier
- Clarivate Analytics Document Solution ID: DL8T0
- PubMed Identifier: 38138481
- Ausgabe der Veröffentlichung
- 24
- Zeitschrift
- MOLECULES
- Schlüsselwörter
- HSA
- STD NMR
- INPHARMA NMR
- docking calculations
- NBD-C-12 FA
- Artikelnummer
- ARTN 7991
- Datum der Veröffentlichung
- 2023
- Status
- Published
- Titel
- NMR and Docking Calculations Reveal Novel Atomistic Selectivity of a Synthetic High-Affinity Free Fatty Acid vs. Free Fatty Acids in Sudlow's Drug Binding Sites in Human Serum Albumin
- Sub types
- Article
- Ausgabe der Zeitschrift
- 28
Datenquelle: Web of Science (Lite)
- Andere Metadatenquellen:
-
- Abstract
- <jats:p>Saturation transfer difference (STD), inter-ligand NOEs (INPHARMA NMR), and docking calculations are reported for investigating specific binding sites of the high-affinity synthetic 7-nitrobenz-2-oxa-1,3-diazoyl-4-C12 fatty acid (NBD-C12 FA) with non-labeled human serum albumin (HSA) and in competition with the drugs warfarin and ibuprofen. A limited number of negative interligand NOEs between NBD-C12 FA and warfarin were interpreted in terms of a short-range allosteric competitive binding in the wide Sudlow’s binding site II (FA7) of NBD-C12 FA with Ser-202, Lys-199, and Trp-214 and warfarin with Arg-218 and Arg-222. In contrast, the significant number of interligand NOEs between NBD-C12 FA and ibuprofen were interpreted in terms of a competitive binding mode in Sudlow’s binding site I (FA3 and FA4) with Ser-342, Arg-348, Arg-485, Arg-410, and Tyr-411. NBD-C12 FA has the unique structural properties, compared to short-, medium-, and long-chain saturated and unsaturated natural free fatty acids, of interacting with well-defined structures with amino acids of both the internal and external polar anchor sites in Sudlow’s binding site I and with amino acids in both FA3 and FA4 in Sudlow’s binding site II. The NBD-C12 FA, therefore, interacts with novel structural characteristics in the drug binding sites I and II and can be regarded as a prototype molecule for drug development.</jats:p>
- Autoren
- Themistoklis Venianakis
- Alexandra Primikyri
- Till Opatz
- Stefan Petry
- Georgios Papamokos
- Ioannis P Gerothanassis
- DOI
- 10.3390/molecules28247991
- eISSN
- 1420-3049
- Ausgabe der Veröffentlichung
- 24
- Zeitschrift
- Molecules
- Sprache
- en
- Online publication date
- 2023
- Paginierung
- 7991 - 7991
- Status
- Published online
- Herausgeber
- MDPI AG
- Herausgeber URL
- http://dx.doi.org/10.3390/molecules28247991
- Datum der Datenerfassung
- 2023
- Titel
- NMR and Docking Calculations Reveal Novel Atomistic Selectivity of a Synthetic High-Affinity Free Fatty Acid vs. Free Fatty Acids in Sudlow’s Drug Binding Sites in Human Serum Albumin
- Ausgabe der Zeitschrift
- 28
Datenquelle: Crossref
- Abstract
- Saturation transfer difference (STD), inter-ligand NOEs (INPHARMA NMR), and docking calculations are reported for investigating specific binding sites of the high-affinity synthetic 7-nitrobenz-2-oxa-1,3-diazoyl-4-C<sub>12</sub> fatty acid (NBD-C<sub>12</sub> FA) with non-labeled human serum albumin (HSA) and in competition with the drugs warfarin and ibuprofen. A limited number of negative interligand NOEs between NBD-C<sub>12</sub> FA and warfarin were interpreted in terms of a short-range allosteric competitive binding in the wide Sudlow's binding site II (FA7) of NBD-C<sub>12</sub> FA with Ser-202, Lys-199, and Trp-214 and warfarin with Arg-218 and Arg-222. In contrast, the significant number of interligand NOEs between NBD-C<sub>12</sub> FA and ibuprofen were interpreted in terms of a competitive binding mode in Sudlow's binding site I (FA3 and FA4) with Ser-342, Arg-348, Arg-485, Arg-410, and Tyr-411. NBD-C<sub>12</sub> FA has the unique structural properties, compared to short-, medium-, and long-chain saturated and unsaturated natural free fatty acids, of interacting with well-defined structures with amino acids of both the internal and external polar anchor sites in Sudlow's binding site I and with amino acids in both FA3 and FA4 in Sudlow's binding site II. The NBD-C<sub>12</sub> FA, therefore, interacts with novel structural characteristics in the drug binding sites I and II and can be regarded as a prototype molecule for drug development.
- Addresses
- Section of Organic Chemistry and Biochemistry, Department of Chemistry, University of Ioannina, GR-45110 Ioannina, Greece.
- Autoren
- Themistoklis Venianakis
- Alexandra Primikyri
- Till Opatz
- Stefan Petry
- Georgios Papamokos
- Ioannis P Gerothanassis
- DOI
- 10.3390/molecules28247991
- eISSN
- 1420-3049
- Externe Identifier
- PubMed Identifier: 38138481
- PubMed Central ID: PMC10745614
- Funding acknowledgements
- Hellenic Foundation for Research and Innovation: 2050
- Hellenic Foundation for Research and Innovation (H.F.R.I.): 2050
- Open access
- true
- ISSN
- 1420-3049
- Ausgabe der Veröffentlichung
- 24
- Zeitschrift
- Molecules (Basel, Switzerland)
- Schlüsselwörter
- Humans
- Ibuprofen
- Warfarin
- Fatty Acids
- Fatty Acids, Nonesterified
- Amino Acids
- Serum Albumin
- Magnetic Resonance Spectroscopy
- Binding Sites
- Protein Binding
- Serum Albumin, Human
- Sprache
- eng
- Medium
- Electronic
- Online publication date
- 2023
- Open access status
- Open Access
- Paginierung
- 7991
- Datum der Veröffentlichung
- 2023
- Status
- Published
- Publisher licence
- CC BY
- Datum der Datenerfassung
- 2023
- Titel
- NMR and Docking Calculations Reveal Novel Atomistic Selectivity of a Synthetic High-Affinity Free Fatty Acid vs. Free Fatty Acids in Sudlow's Drug Binding Sites in Human Serum Albumin.
- Sub types
- research-article
- Journal Article
- Ausgabe der Zeitschrift
- 28
Files
https://europepmc.org/articles/PMC10745614?pdf=render
Datenquelle: Europe PubMed Central
- Abstract
- Saturation transfer difference (STD), inter-ligand NOEs (INPHARMA NMR), and docking calculations are reported for investigating specific binding sites of the high-affinity synthetic 7-nitrobenz-2-oxa-1,3-diazoyl-4-C12 fatty acid (NBD-C12 FA) with non-labeled human serum albumin (HSA) and in competition with the drugs warfarin and ibuprofen. A limited number of negative interligand NOEs between NBD-C12 FA and warfarin were interpreted in terms of a short-range allosteric competitive binding in the wide Sudlow's binding site II (FA7) of NBD-C12 FA with Ser-202, Lys-199, and Trp-214 and warfarin with Arg-218 and Arg-222. In contrast, the significant number of interligand NOEs between NBD-C12 FA and ibuprofen were interpreted in terms of a competitive binding mode in Sudlow's binding site I (FA3 and FA4) with Ser-342, Arg-348, Arg-485, Arg-410, and Tyr-411. NBD-C12 FA has the unique structural properties, compared to short-, medium-, and long-chain saturated and unsaturated natural free fatty acids, of interacting with well-defined structures with amino acids of both the internal and external polar anchor sites in Sudlow's binding site I and with amino acids in both FA3 and FA4 in Sudlow's binding site II. The NBD-C12 FA, therefore, interacts with novel structural characteristics in the drug binding sites I and II and can be regarded as a prototype molecule for drug development.
- Date of acceptance
- 2023
- Autoren
- Themistoklis Venianakis
- Alexandra Primikyri
- Till Opatz
- Stefan Petry
- Georgios Papamokos
- Ioannis P Gerothanassis
- Autoren-URL
- https://www.ncbi.nlm.nih.gov/pubmed/38138481
- DOI
- 10.3390/molecules28247991
- eISSN
- 1420-3049
- Externe Identifier
- PubMed Central ID: PMC10745614
- Funding acknowledgements
- Hellenic Foundation for Research and Innovation (H.F.R.I.): 2050
- Ausgabe der Veröffentlichung
- 24
- Zeitschrift
- Molecules
- Schlüsselwörter
- HSA
- INPHARMA NMR
- NBD-C12 FA
- STD NMR
- docking calculations
- Humans
- Serum Albumin, Human
- Fatty Acids, Nonesterified
- Serum Albumin
- Ibuprofen
- Protein Binding
- Warfarin
- Binding Sites
- Fatty Acids
- Magnetic Resonance Spectroscopy
- Amino Acids
- Sprache
- eng
- Country
- Switzerland
- PII
- molecules28247991
- Datum der Veröffentlichung
- 2023
- Status
- Published online
- Datum, an dem der Datensatz öffentlich gemacht wurde
- 2023
- Titel
- NMR and Docking Calculations Reveal Novel Atomistic Selectivity of a Synthetic High-Affinity Free Fatty Acid vs. Free Fatty Acids in Sudlow's Drug Binding Sites in Human Serum Albumin.
- Sub types
- Journal Article
- Ausgabe der Zeitschrift
- 28
Datenquelle: PubMed
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