title: Biophysical and molecular docking insight into interaction mechanism and thermal stability of human serum albumin isoforms with a semi-synthetic water-soluble camptothecin analog irinotecan hydrochloride.
abstract: In the present work, we have examined the binding parameters, thermodynamics, and stability of human serum albumin (HSA) isoforms at pH 7.4 and 9.0, using spectroscopic, calorimetric, and molecular docking methods in the presence of water-soluble camptothecin analog irinotecan hydrochloride (CPT-11). We observed that CPT-11 binds to HSA through a static quenching procedure of ground-state complex formation with N-isoform and B-isoform. Hydrogen bond and hydrophobic interactions are the major governing forces that participating in the formation of protein-drug complex. To determine the binding site of CPT-11 within HSA molecules, we also have performed molecular docking experiments. We explored the CPT-11-mediated stability and modulation of HSA by performing dynamic light scattering (DLS) and differential scanning calorimetry (DSC) experiments. DLS and DSC techniques are used to determine the size and the melting point (Tm) of HSA, which was decreased in the presence of CPT-11. Therefore, CPT-11 plays an important role in HSA stability and protein-ligand interactions. The present study provides valuable information in the field of pharmacokinetics, pharmaco-dynamics, and drug discovery.
authors: a Protein Biophysics Laboratory, Interdisciplinary Biotechnology Unit , Aligarh Muslim University , Aligarh 202002 , India.
authors: Mohd
authors: M
authors: Ishtikhar
authors: a Protein Biophysics Laboratory, Interdisciplinary Biotechnology Unit , Aligarh Muslim University , Aligarh 202002 , India.
authors: Mohsin Vahid
authors: MV
authors: Khan
authors: b School of Computational & Integrative Sciences , Jawaharlal Nehru University , New Delhi 110067 , India.
authors: Shawez
authors: S
authors: Khan
authors: a Protein Biophysics Laboratory, Interdisciplinary Biotechnology Unit , Aligarh Muslim University , Aligarh 202002 , India.
authors: Sumit Kumar
authors: SK
authors: Chaturvedi
authors: c Laboratory of Immunology and Molecular Physiology, Faculty of Science, Zoology Department , Assiut University , Assiut 71516 , Egypt.
authors: Gamal
authors: G
authors: Badr
authors: d Deanship of Scientific Research , King Saud University , Riyadh , Saudi Arabia.|e Food Science and Nutrition Department , National Research Center , Dokki, Cairo , Egypt.
authors: Mohamed H
authors: MH
authors: Mahmoud
authors: a Protein Biophysics Laboratory, Interdisciplinary Biotechnology Unit , Aligarh Muslim University , Aligarh 202002 , India.
authors: Rizwan Hasan
authors: RH
authors: Khan
mesh_terms: D002166:Camptothecin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D000077146:Irinotecan; D007700:Kinetics; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D011485:Protein Binding; D055550:Protein Stability; D012709:Serum Albumin / Q000737:chemistry* / Q000378:metabolism; D013057:Spectrum Analysis; D013816:Thermodynamics
chemical_list: D012709:Serum Albumin; D000077146:Irinotecan; D002166:Camptothecin
keywords: anticancerous drug; camptothecin; differential scanning calorimetry; dynamic light scattering; human serum albumin; irinotecan hydrochloride; isothermal titration calorimetry; protein–drug interaction