Unravelling the interaction of glipizide with human serum albumin using various spectroscopic techniques and molecular dynamics studies
| Autor: | Tasneem Fatma, Saleh M Alosaimi, Razique Anwer, Pallavi Somvanshi, Shafiul Haque, Nazia Ahmad, Khalid I. Al-Qumaizi |
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| Rok vydání: | 2020 |
| Předmět: |
Drug
Circular dichroism medicine.drug_class media_common.quotation_subject 030303 biophysics Serum Albumin Human Type 2 diabetes Pharmacology Molecular Dynamics Simulation 03 medical and health sciences Molecular dynamics Structural Biology medicine Humans Tissue Distribution Molecular Biology media_common 0303 health sciences Binding Sites Chemistry Circular Dichroism General Medicine medicine.disease Human serum albumin Sulfonylurea body regions Molecular Docking Simulation medicine.anatomical_structure Spectrometry Fluorescence Diabetes Mellitus Type 2 embryonic structures Thermodynamics Pancreas Glipizide medicine.drug Protein Binding |
| Zdroj: | Journal of biomolecular structuredynamics. 39(1) |
| ISSN: | 1538-0254 |
| Popis: | Glipizide is known to stimulate insulin secretion by β-cells of the pancreas. It is a second-generation sulfonylurea drug used in the management of type 2 diabetes. The shorter biological half-life makes it a suitable candidate to be designed as a controlled release formulation. Human serum albumin (HSA), a major plasma protein plays a crucial role in the transportation of drugs, hormones, fatty acids, and many other molecules and determines their physiological fate and biodistribution. In this study, the interaction of glipizide with HSA was investigated under physiological conditions using multi-spectroscopic techniques corroborated with molecular docking and dynamics approach. It was found that glipizide integrates to HSA with a binding constant in the order of 105 M−1. The mode of fluorescence quenching by glipizide is static in nature with one binding site. Glipizide preferentially interacts with sub-domain IIA of HSA and their complexion is thermodynamically favorable. This interaction results in the loss of α-helical content of HSA. The energy transfer efficiency from HSA to glipizide was found to be 26.72%. In silico molecular docking and simulation studies ratified in vitro findings and revealed that hydrogen bonds and hydrophobic interactions are accountable for glipizide-HSA complex formation. Communicated by Ramaswamy H. Sarma |
| Databáze: | OpenAIRE |
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