Biophysical characterization of human serum albumin interaction with dapagliflozin: multi-spectroscopic and molecular docking study
Human serum albumin (HSA) is the most abundant protein in human blood plasma and plays a crucial role in drug transport and pharmacokinetics. Dapagliflozin (DAPA), a sodium-glucose co-transporter 2 (SGLT2) inhibitor, is widely prescribed for the treatment of type 2 diabetes mellitus. In the present...
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Mongolian Academy of Sciences
2025-03-01
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| Series: | Proceedings of the Mongolian Academy of Sciences |
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| author | Tuvshinjargal Duurenjargal Tuguldur Badamkhatan Khurelbaatar Luvsanbat Mishig-Ochir Tsogbadrakh Urnukhsaikhan Enerelt |
| author_facet | Tuvshinjargal Duurenjargal Tuguldur Badamkhatan Khurelbaatar Luvsanbat Mishig-Ochir Tsogbadrakh Urnukhsaikhan Enerelt |
| author_sort | Tuvshinjargal Duurenjargal |
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| description | Human serum albumin (HSA) is the most abundant protein in human blood plasma and plays a crucial role in drug transport and pharmacokinetics. Dapagliflozin (DAPA), a sodium-glucose co-transporter 2 (SGLT2) inhibitor, is widely prescribed for the treatment of type 2 diabetes mellitus. In the present study, we employed a combination of multi-spectroscopic techniques, including fluorescence spectroscopy (three-dimensional, synchronous), UV-visible absorption spectroscopy, thermodynamic analysis, and molecular docking to investigate the interaction of dapagliflozin with HSA under physiological condition. The quenching mechanism of DAPA was determined to be dynamic through Stern-Volmer and modified Stern-Volmer analyses. The binding constants at 298 K, 303 K, 308 K were 0.52x104, 0.303x104 and 0.264x104 M-1, respectively. Thermodynamic analysis revealed that the binding process is spontaneous, driven primarily by hydrogen bonding and hydrophobic interactions at various temperatures. Synchronous fluorescence studies suggest that DAPA binding does not significantly alter the microenvironment around the tyrosine and tryptophan residues of HSA, implying that the binding sites are spatially distinct from these residues. Three-dimensional fluorescence studies reveal that the addition of DAPA to HSA affects changes in the micro-environment and conformation of HSA. UV-VIS spectroscopy confirmed the formation of the HSA-DAPA complex, characterized by spectral shifts in both peptide bond and aromatic amino acid regions, indicating alterations in the protein's secondary structure. The decrease in zeta potential upon DAPA binding suggests a change in the surface charge and potential conformational changes in HSA, which may influence its biological activity and interaction with other molecules. Molecular docking studies identified key amino acid residues involved in the binding of DAPA to HSA, primarily through hydrophobic and hydrogen bond interactions. |
| format | Article |
| id | doaj-art-ccfb9b11d417490fa85f1d9c1594d6f6 |
| institution | Kabale University |
| issn | 2310-4716 2312-2994 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Mongolian Academy of Sciences |
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| series | Proceedings of the Mongolian Academy of Sciences |
| spelling | doaj-art-ccfb9b11d417490fa85f1d9c1594d6f62025-08-20T03:25:27ZengMongolian Academy of SciencesProceedings of the Mongolian Academy of Sciences2310-47162312-29942025-03-01132810.5564/pmas.v65i01.42034154Biophysical characterization of human serum albumin interaction with dapagliflozin: multi-spectroscopic and molecular docking studyTuvshinjargal Duurenjargal0https://orcid.org/0009-0007-9384-7516Tuguldur Badamkhatan1https://orcid.org/0000-0002-4677-9326Khurelbaatar Luvsanbat2https://orcid.org/0000-0002-0729-8546Mishig-Ochir Tsogbadrakh3https://orcid.org/0000-0002-5065-8295Urnukhsaikhan Enerelt4https://orcid.org/0000-0003-4484-4267Department of Biology, School of Arts and Sciences, National University of Mongolia, Ulaanbaatar, MongoliaRadiation biophysics laboratory, Institute of Physics and Technology, Mongolian Academy of Sciences, Ulaanbaatar, MongoliaRadiation biophysics laboratory, Institute of Physics and Technology, Mongolian Academy of Sciences, Ulaanbaatar, MongoliaDepartment of Biology, School of Arts and Sciences, National University of Mongolia, Ulaanbaatar, MongoliaDepartment of Biology, School of Arts and Sciences, National University of Mongolia, Ulaanbaatar, MongoliaHuman serum albumin (HSA) is the most abundant protein in human blood plasma and plays a crucial role in drug transport and pharmacokinetics. Dapagliflozin (DAPA), a sodium-glucose co-transporter 2 (SGLT2) inhibitor, is widely prescribed for the treatment of type 2 diabetes mellitus. In the present study, we employed a combination of multi-spectroscopic techniques, including fluorescence spectroscopy (three-dimensional, synchronous), UV-visible absorption spectroscopy, thermodynamic analysis, and molecular docking to investigate the interaction of dapagliflozin with HSA under physiological condition. The quenching mechanism of DAPA was determined to be dynamic through Stern-Volmer and modified Stern-Volmer analyses. The binding constants at 298 K, 303 K, 308 K were 0.52x104, 0.303x104 and 0.264x104 M-1, respectively. Thermodynamic analysis revealed that the binding process is spontaneous, driven primarily by hydrogen bonding and hydrophobic interactions at various temperatures. Synchronous fluorescence studies suggest that DAPA binding does not significantly alter the microenvironment around the tyrosine and tryptophan residues of HSA, implying that the binding sites are spatially distinct from these residues. Three-dimensional fluorescence studies reveal that the addition of DAPA to HSA affects changes in the micro-environment and conformation of HSA. UV-VIS spectroscopy confirmed the formation of the HSA-DAPA complex, characterized by spectral shifts in both peptide bond and aromatic amino acid regions, indicating alterations in the protein's secondary structure. The decrease in zeta potential upon DAPA binding suggests a change in the surface charge and potential conformational changes in HSA, which may influence its biological activity and interaction with other molecules. Molecular docking studies identified key amino acid residues involved in the binding of DAPA to HSA, primarily through hydrophobic and hydrogen bond interactions.https://www.mongoliajol.info/index.php/PMAS/article/view/4203dapagliflozinhuman serum albuminmulti-spectroscopyzeta-potentialmolecular docking |
| spellingShingle | Tuvshinjargal Duurenjargal Tuguldur Badamkhatan Khurelbaatar Luvsanbat Mishig-Ochir Tsogbadrakh Urnukhsaikhan Enerelt Biophysical characterization of human serum albumin interaction with dapagliflozin: multi-spectroscopic and molecular docking study Proceedings of the Mongolian Academy of Sciences dapagliflozin human serum albumin multi-spectroscopy zeta-potential molecular docking |
| title | Biophysical characterization of human serum albumin interaction with dapagliflozin: multi-spectroscopic and molecular docking study |
| title_full | Biophysical characterization of human serum albumin interaction with dapagliflozin: multi-spectroscopic and molecular docking study |
| title_fullStr | Biophysical characterization of human serum albumin interaction with dapagliflozin: multi-spectroscopic and molecular docking study |
| title_full_unstemmed | Biophysical characterization of human serum albumin interaction with dapagliflozin: multi-spectroscopic and molecular docking study |
| title_short | Biophysical characterization of human serum albumin interaction with dapagliflozin: multi-spectroscopic and molecular docking study |
| title_sort | biophysical characterization of human serum albumin interaction with dapagliflozin multi spectroscopic and molecular docking study |
| topic | dapagliflozin human serum albumin multi-spectroscopy zeta-potential molecular docking |
| url | https://www.mongoliajol.info/index.php/PMAS/article/view/4203 |
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