title: Interaction between Human Serum Albumin and antidiabetic compounds and its influence on the O2((1)Δg)-mediated degradation of the protein.
abstract: The complexity depicted by disease scenarios as diabetes mellitus, constitutes a very interesting field of study when drugs and biologically relevant components may be affected by such environments. In this report, the interaction between the protein Human Serum Albumin (HSA) and two antidiabetics (Andb), Gliclazide (Gli) and Glipizide (Glip) was studied through fluorescence and docking assays, in order to characterize these systems. On the basis that HSA and Andb can be exposed in vivo at high Reactive Oxygen Species (ROS) concentrations in diabetic patients, the degradative process of the protein free and bound to Andb, in presence of the species singlet molecular oxygen (O2((1)Δg)), was evaluated. Fluorescence and docking assays indicated that Gli, as well as Glip bind to HSA on two sites, with binding constants values in the order of 10(4)-10(5)M(-1). Likewise, docking assays revealed that the location of Gli or Glip on the protein may be the HSA binding sites II and III. Thermodynamic parameters showed that the interaction between HSA and Glip is a favored, enthalpically-controlled process. Oxygen uptake experiments indicated that Glip is less photooxidizable than Gli through a O2((1)Δg)-mediated process. Besides, the protein-Andb binding produced a decrease in the overall rate constant for O2((1)Δg) quenching as compared to the value for the free protein. This fact could be interpreted in terms of a reduction in the availability of Tyrosine residues in the bonded protein, with a concomitant decrease in the physical quenching deactivation of the oxidative species.
authors.affiliation: Departamento de Química, Universidad Nacional de Río Cuarto, X5804BYA Córdoba, Argentina. Electronic address: cchallier@exa.unrc.edu.ar.
authors.forename: C
authors.initials: C
authors.lastname: Challier
authors.affiliation: Departamento de Biología Molecular, Universidad Nacional de Río Cuarto, X5804BYA Córdoba, Argentina.
authors.forename: P
authors.initials: P
authors.lastname: Beassoni
authors.affiliation: Departamento de Biología Molecular, Universidad Nacional de Río Cuarto, X5804BYA Córdoba, Argentina.
authors.forename: C
authors.initials: C
authors.lastname: Boetsch
authors.affiliation: Departamento de Química, Universidad Nacional de Río Cuarto, X5804BYA Córdoba, Argentina.
authors.forename: N A
authors.initials: NA
authors.lastname: García
authors.affiliation: Departamento de Química, Universidad Nacional de Río Cuarto, X5804BYA Córdoba, Argentina.
authors.forename: M A
authors.initials: MA
authors.lastname: Biasutti
authors.affiliation: Departamento de Química, Universidad Nacional de Río Cuarto, X5804BYA Córdoba, Argentina. Electronic address: scriado@exa.unrc.edu.ar.
authors.forename: S
authors.initials: S
authors.lastname: Criado
mesh_terms: D001665:Binding Sites; D005907:Gliclazide / Q000737:chemistry* / Q000378:metabolism; D005913:Glipizide / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000737:chemistry* / Q000378:metabolism; D008027:Light; D062105:Molecular Docking Simulation; D010084:Oxidation-Reduction; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D017382:Reactive Oxygen Species / Q000737:chemistry / Q000378:metabolism; D012709:Serum Albumin / Q000737:chemistry* / Q000378:metabolism; D026082:Singlet Oxygen / Q000737:chemistry*; D013050:Spectrometry, Fluorescence; D013816:Thermodynamics
chemical_list: D007004:Hypoglycemic Agents; D017382:Reactive Oxygen Species; D012709:Serum Albumin; D026082:Singlet Oxygen; D005907:Gliclazide; D005913:Glipizide