title: Comprehensive insight into the binding of sunitinib, a multi-targeted anticancer drug to human serum albumin.
abstract: Binding studies between a multi-targeted anticancer drug, sunitinib (SU) and human serum albumin (HSA) were made using fluorescence, UV-vis absorption, circular dichroism (CD) and molecular docking analysis. Both fluorescence quenching data and UV-vis absorption results suggested formation of SU-HSA complex. Moderate binding affinity between SU and HSA was evident from the value of the binding constant (3.04×104M-1), obtained at 298K. Involvement of hydrophobic interactions and hydrogen bonds as the leading intermolecular forces in the formation of SU-HSA complex was predicted from the thermodynamic data of the binding reaction. These results were in good agreement with the molecular docking analysis. Microenvironmental perturbations around Tyr and Trp residues as well as secondary and tertiary structural changes in HSA upon SU binding were evident from the three-dimensional fluorescence and circular dichroism results. SU binding to HSA also improved the thermal stability of the protein. Competitive displacement results and molecular docking analysis revealed the binding locus of SU to HSA in subdomain IIA (Sudlow's site I). The influence of a few common ions on the binding constant of SU-HSA complex was also noticed.
authors.affiliation: Biomolecular Research Group, Biochemistry Programme, Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Md Zahirul
authors.initials: MZ
authors.lastname: Kabir
authors.affiliation: Bioinformatics Programme, Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Wei-Ven
authors.initials: WV
authors.lastname: Tee
authors.affiliation: Bioinformatics Programme, Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia; Centre of Research for Computational Sciences and Informatics for Biology, Bioindustry, Environment, Agriculture and Healthcare, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Saharuddin B
authors.initials: SB
authors.lastname: Mohamad
authors.affiliation: Biomolecular Research Group, Biochemistry Programme, Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Zazali
authors.initials: Z
authors.lastname: Alias
authors.affiliation: Biomolecular Research Group, Biochemistry Programme, Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia; Centre of Research for Computational Sciences and Informatics for Biology, Bioindustry, Environment, Agriculture and Healthcare, University of Malaya, Kuala Lumpur, Malaysia. Electronic address: saadtayyab2004@um.edu.my.
authors.forename: Saad
authors.initials: S
authors.lastname: Tayyab
mesh_terms: D000970:Antineoplastic Agents / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D007211:Indoles / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D062105:Molecular Docking Simulation; D011485:Protein Binding; D011758:Pyrroles / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D000075462:Serum Albumin, Human / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D000077210:Sunitinib; D013816:Thermodynamics
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib; D000075462:Serum Albumin, Human
keywords: Fluorescence quenching; Human serum albumin; Ligand–protein interaction; Molecular docking; Sunitinib