title: The investigation of the binding of 6-mercaptopurine to site I on human serum albumin.
abstract: 6-Mercaptopurine (6-MP) is one of a large series of purine analogues which has been found active against human leukemias. The equilibrium dialysis, circular dichroism (CD) and molecular docking were employed to study the binding of 6-MP to human serum albumin (HSA). The binding of 6-MP to HSA in the equilibrium dialysis experiment was detected by measuring the displacement of 6-MP by specific markers for site I on HSA, warfarin (RWF), phenylbutazone (PhB) and n-butyl p-aminobenzoate (ABE). It was shown, according to CD data, that binding of 6-MP to HSA leads to alteration of HSA secondary structure. Based on the findings from displacement experiment and molecular docking simulation it was found that 6-MP was located within binding cavity of subdomain IIA and the space occupied by site markers overlapped with that of 6-MP. Displacement of 6-MP by the RWF or PhB was not up the level expected for a competitive mechanism, therefore displacement of 6-MP was rather by non-cooperative than that the direct competition. Instead, in case of the interaction between ABE and 6-MP, when the little enhancement of the binding of ABE by 6-MP was found, the interaction could be via a positively cooperative mechanism.
authors.affiliation: Department of General and Inorganic Chemistry, The School of Pharmacy and Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia, Sosnowiec, Poland. jsochacka@sum.edu.pl
authors.forename: Jolanta
authors.initials: J
authors.lastname: Sochacka
authors.forename: Wojciech
authors.initials: W
authors.lastname: Baran
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D000838:Anions / Q000737:chemistry; D001665:Binding Sites; D002942:Circular Dichroism; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D015122:Mercaptopurine / Q000737:chemistry* / Q000378:metabolism*; D062105:Molecular Docking Simulation; D000091402:Prohibitins; D011485:Protein Binding; D012709:Serum Albumin / Q000737:chemistry* / Q000378:metabolism*; D013056:Spectrophotometry, Ultraviolet; D013816:Thermodynamics
chemical_list: D000596:Amino Acids; D000838:Anions; C000717328:PHB protein, human; D000091402:Prohibitins; D012709:Serum Albumin; D015122:Mercaptopurine