title: Effect of guanidine hydrochloride and urea on the interaction of 6-thioguanine with human serum albumin: a spectroscopic and molecular dynamics based study.
abstract: 6-thioguanine (6-TG) is an antineoplastic, nucleobase guanine, purine analog drug belongs to thiopurine drug-family of antimetabolites. In the present study, we report an experimental approach towards interaction mechanism of 6-TG with human serum albumin (HSA) and examine the chemical stability of HSA in the presence of denaturants such as guanidine hydrochloride (GdnHCl) and urea. Interaction of 6-TG with HSA has been studied by various spectroscopic and spectropolarimeteric methods to investigate what short of binding occurs at physiological conditions. 6-TG binds in the hydrophobic cavity of subdomain IIA of HSA by static quenching mechanism which induces conformation alteration in the protein structure. That helpful for further study of denaturation process where change in secondary structures causes unfolding of protein that also responsible for severance of domain III from rest of the protein part. We have also performed molecular simulation and molecular docking study in the presence of denaturating agents to determine the binding property of 6-TG and the effect of denaturating agents on the structural activity of HSA. We had found that GdnHCl is more effective denaturating agent when compared to urea. Hence, this study provides straight evidence of the binding mechanism of 6-TG with HSA and the formation of intermediate or unfolding transition that causes unfolding of HSA.
authors.affiliation: a Interdisciplinary Biotechnology Unit , Aligarh Muslim University , Aligarh 202002 , India.
authors.forename: Mohd
authors.initials: M
authors.lastname: Ishtikhar
authors.affiliation: b Faculty of Engineering, Department of Bioengineering , Integral University , Lucknow 226026 , India.
authors.forename: Anam
authors.initials: A
authors.lastname: Khan
authors.affiliation: c Department of Chemical Engineering , National Taiwan University , Taipei 10617 , Taiwan.
authors.forename: Chih-Kai
authors.initials: CK
authors.lastname: Chang
authors.affiliation: c Department of Chemical Engineering , National Taiwan University , Taipei 10617 , Taiwan.
authors.forename: Lilian Tsai-Wei
authors.initials: LT
authors.lastname: Lin
authors.affiliation: c Department of Chemical Engineering , National Taiwan University , Taipei 10617 , Taiwan.
authors.forename: Steven S-S
authors.initials: SS
authors.lastname: Wang
authors.affiliation: a Interdisciplinary Biotechnology Unit , Aligarh Muslim University , Aligarh 202002 , India.
authors.forename: Rizwan Hasan
authors.initials: RH
authors.lastname: Khan
mesh_terms: D019791:Guanidine / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D008968:Molecular Conformation; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D011489:Protein Denaturation / Q000187:drug effects; D017510:Protein Folding / Q000187:drug effects; D012709:Serum Albumin / Q000737:chemistry*; D013057:Spectrum Analysis; D013329:Structure-Activity Relationship; D013866:Thioguanine / Q000737:chemistry* / Q000494:pharmacology; D014508:Urea / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D012709:Serum Albumin; D014508:Urea; D013866:Thioguanine; D019791:Guanidine
keywords: 6-thioguanine; circular dichroism; fluorescence spectroscopy; guanidine hydrochloride denaturation; human serum albumin; molecular dynamics; urea denaturation