Exploring the binding interactions of structurally diverse dichalcogenoimidodiphosphinate ligands with α-amylase: Spectroscopic approach coupled with molecular docking
| dc.contributor.author | Dairo, Oluropo | |
| dc.date.accessioned | 2022-04-29T16:47:15Z | |
| dc.date.available | 2022-04-29T16:47:15Z | |
| dc.date.issued | 2020 | |
| dc.description.abstract | Postprandial hyperglycemia has orchestrated untimely death among diabetic patients over the decades and regulation of α-amylase activity is now becoming a promising management option for type 2 diabetes. The present study investigated the binding interactions of three structurally diverse dichalcogenoimidodiphosphinate ligands with α-amylase to ascertain the affinity of the ligands for α-amylase using spectroscopic and molecular docking methods. The ligands were characterized using 1H and 31P NMR spectroscopy and CHN analysis. Dis- elenoimidodiphosphinate ligand (DY300), dithioimidodiphosphinate ligand (DY301), and thio- selenoimidodiphosphinate ligand (DY302) quenched the intrinsic fluorescence intensity of α-amylase via a static quenching mechanism with bimolecular quenching constant (Kq) values in the order of x1011 M-1s-1, indicating formation of enzyme-ligand complexes. A binding stoichiometry of n≈1 was observed for α-amylase, with high binding constants (Ka). α-Amylase inhibition was as follow: Acarbose>DY301>DY300>DY302. Values of thermodynamic parameters obtained at temperatures investigated (298, 304 and 310 K) revealed spontaneous complex formation (ΔG<0) between the ligands and α-amylase; the main driving forces were hydrophobic in- teractions (with DY300, DY301, except DY302). UV–visible spectroscopy and Fo ̈rster resonance energy transfer (FRET) affirmed change in enzyme conformation and binding occurrence. Molecular docking revealed ligands interaction with α-amylase via some key catalytic site amino acid residues (Asp197, Glu233 and Asp300). DY301 perhaps showed highest α-amylase inhibition (IC50, 268.11 ± 0.74 μM) due to its moderately high affinity and composition of two sulphide bonds unlike the others. This study might provide theoretical basis for development of novel α-amylase inhibitors from dichalcogenoimidodiphosphinate ligands for management of postprandial hyperglycemia. | en_US |
| dc.description.sponsorship | Financial support was provided by Elsevier Foundation, with grant number: BBREPAEAx0nHYATS_BG. | en_US |
| dc.identifier.citation | Avwioroko, O.J., Oyetunde, T.T., Atanu, F.O., Otuechere, C.A., Anigboro, A.A., Dairo, O.F., Ejoh, A.S., Ajibade, S.O. and Omorogie, M.O. (2020) Exploring the binding interactions of structurally diverse dichalcogenoimidodiphosphinate ligands with α-amylase: Spectroscopic approach coupled with molecular docking, Biochemistry and Biophysics Reports, 24: 100837. | en_US |
| dc.identifier.uri | http://dspace.run.edu.ng:8080/jspui/handle/123456789/2553 | |
| dc.language.iso | en | en_US |
| dc.publisher | Elsevier | en_US |
| dc.subject | α-Amylase inhibition | en_US |
| dc.subject | Ligand-protein binding | en_US |
| dc.subject | Spectroscopy | en_US |
| dc.subject | Hyperglycemia | en_US |
| dc.subject | Anti-diabetic agents | en_US |
| dc.title | Exploring the binding interactions of structurally diverse dichalcogenoimidodiphosphinate ligands with α-amylase: Spectroscopic approach coupled with molecular docking | en_US |
| dc.type | Article | en_US |