Thermodynamic Characterization of the Binding Process of Sulindac to Human Serum Albumin

Zhivkova, Zvetanka; Russeva, Veska N.

doi:10.1055/s-0031-1297070

Cited by 4 publications

(5 citation statements)

References 8 publications

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“…Nearly 15 % of the retention of PBZ is due to the competitive binding with SUL. The relationship between 1/(k'-X) and [SUL] in the mobile phase is linear till [SUL] of 4 µmol/l which coincides with the concentration of SUL-binding sites previously reported (4.5−4.7 × 10 -6 mol/l) [5]. This behavior suggests a single site competition between PBZ and SUL for these sites.…”

Section: Competition Between Sul and Pbzsupporting

confidence: 88%

“…3, and their linearity is an indication that the standard enthalpy change is essentially constant over the investigated temperature range. The binding characteristics of SUL and PBZ during their competitive binding are presented in Table 1 together with the respective values for SUL in the absence of PBZ [5].…”

Section: Competition Between Sul and Pbzmentioning

confidence: 99%

“…Using specific markers for the major binding areas on HSA − phenylbutazone for Site I and diazepam for Site II − equal affinity constants of 1.3 × 10 5 l/ mol for the high-affinity phenylbutazone and diazepam binding sites, as well as a value of 4.2 × 10 3 l/mol for the low-affinity diazepam binding sites are determined [4]. An attempt to clarify the molecular basis of sulindac-HSA binding is made using the temperature dependence of the affinity constants and thermodynamic cal- culations [5]. So far no data are available for the interactions of sulindac with other drugs on protein binding level.…”

Section: Introductionmentioning

confidence: 99%

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Molecular Basis of Sulindac Competition with Specific Markers for the Major Binding Sites on Human Serum Albumin

Russeva¹,

Zhivkova²

2011

Arzneimittelforschung

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This study deals with the competitive interactions of sulindac (CAS 38194-50-2) with specific markers for the major binding areas on human serum albumin (HSA): phenylbutazone (CAS 50-33-9) and warfarin (CAS 129-06-6) for Site I, and diazepam (CAS 439-14-5) for Site II. The method used is high-performance liquid affinity chromatography with HSA-immobilized stationary phase. The affinity constants during the cobinding are determined, and the major thermodynamic parameters are calculated. Based on that the nature of the intermolecular interactions involved in the binding process is hypothesized. The cobinding of sulindac and phenylbutazone is simple competitive and is dominated by hydrogen bonds. The binding affinity of sulindac is significantly decreased by R-warfarin (anticooperative binding), and conformational changes resulting in alteration of the binding mechanisms (electrostatic as well as hydrophobic interactions) are supposed. S-Warfarin hardly affects the binding affinity of sulindac. Sulindac competes with diazepam for two types of binding site: high affinity Site II where the cobinding seems to be dominated by hydrophobic bonding, and low affinity Site I, the latter affinity being significantly decreased (anticooperative binding). These results contribute to a better understanding of the molecular mechanisms of the binding of the investigated drugs with HSA.

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Section: Competition Between Sul and Pbzsupporting

confidence: 88%

Section: Competition Between Sul and Pbzmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Molecular Basis of Sulindac Competition with Specific Markers for the Major Binding Sites on Human Serum Albumin

Russeva¹,

Zhivkova²

2011

Arzneimittelforschung

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“…Thermodynamic study on the binding of sulindac to HSA by means of HPLAC suggested spontaneous binding with a high negative G. Both H and S were negative, and the absolute value of H highly exceeded the entropy term T S. Therefore it was supposed that the binding was dominated by hydrogen bonds and salt linkages while hydrophobic interactions were of less importance. These data allowed hypothesis to be made about the nature of the binding site and the binding mechanism [103,144]. Thermodynamic study also revealed different binding mechanisms for R-and S-WAR, responsible for the observed stereodiscrimination by the common binding site on HSA [144].…”

Section: Thermodynamic Characterization Of Drug -Hsa Bindingmentioning

confidence: 93%

Studies on Drug – Human Serum Albumin Binding: The Current State of the Matter

Zhivkova

2015

CPD

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Human serum albumin (HSA) is the major plasma protein with vital functions acting as depot and career for many endogenous (fatty acids, bilirubin, etc.) and exogenous substances (drugs, nutrients, etc.) in the blood. Binding to HSA controls the free, active concentration of the drug and may affect considerably the overall pharmacodynamic and pharmacokinetic profile. Studies on drug - protein binding are important from both theoretical and practical point of view as they allow better understanding of the processes underlying drug disposition and elimination and the effect of several pathological states or co-administered drugs on drug delivery and efficacy. The present review focuses on the current state of drug - HSA binding studies. The major functions and consequences of drug - protein binding are described. The X-ray structure of HSA is discussed focusing on the location and the architecture of the primary drug and fatty acids binding sites. Some of the most commonly used methods for drug - HSA binding assay are presented together with examples for their application. The most extensive studied topics in the area are discussed including quantitative characterization of drug - HSA complexation, identification of the binding sites, stereoselectivity of drug - HSA interactions, and thermodynamic characterization of the binding process. A short section is devoted to in silico prediction of drug - HSA binding as an important step in drug design and development.

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“…The separation temperature is one of the main determinant factors that can affect selectivity, resolution, retention factor and even the elution order of enantiomers during HPLC enantioseparations [34,35]. To investigate the effects of temperature and to gain a better understanding of the mechanistic aspects of the enantiodiscrimination process on the Chiral-HSA column, thermodynamic analysis was performed in a 10 mM phosphate buffer/IPA 96/4 v/v% mixture.…”

Section: Effect Of the Temperature-thermodynamic Analysismentioning

confidence: 99%

Enantioselective Human Serum Albumin Binding of Apremilast: Liquid Chromatographic, Fluorescence and Molecular Docking Study

Dombi

Horváth

Fiser

et al. 2023

IJMS

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The interaction between human serum albumin (HSA) and apremilast (APR), a novel antipsoriatic drug, was characterized by multimodal analytical techniques including high-performance liquid chromatography (HPLC), fluorescence spectroscopy and molecular docking for the first time. Using an HSA chiral stationary phase, the APR enantiomers were well separated, indicating enantioselective binding between the protein and the analytes. The influence of chromatographic parameters—type and concentration of the organic modifier, buffer type, pH, ionic strength of the mobile phase, flow rate and column temperature—on the chromatographic responses (retention factor and selectivity) was analyzed in detail. The results revealed that the eutomer S-APR bound to the protein to a greater extent than the antipode. The classical van ’t Hoff method was applied for thermodynamic analysis, which indicated that the enantioseparation was enthalpy-controlled. The stability constants of the protein–enantiomer complexes, determined by fluorescence spectroscopy, were in accordance with the elution order observed in HPLC (KR-APR-HSA = 6.45 × 103 M−1, KS-APR-HSA = 1.04 × 104 M−1), showing that, indeed, the later-eluting S-APR displayed a stronger binding with HSA. Molecular docking was applied to study and analyze the interactions between HSA and the APR enantiomers at the atomic level. It was revealed that the most favored APR binding occurred at the border between domains I and II of HSA, and secondary interactions were responsible for the different binding strengths of the enantiomers.

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Thermodynamic Characterization of the Binding Process of Sulindac to Human Serum Albumin

Cited by 4 publications

References 8 publications

Molecular Basis of Sulindac Competition with Specific Markers for the Major Binding Sites on Human Serum Albumin

Molecular Basis of Sulindac Competition with Specific Markers for the Major Binding Sites on Human Serum Albumin

Studies on Drug – Human Serum Albumin Binding: The Current State of the Matter

Enantioselective Human Serum Albumin Binding of Apremilast: Liquid Chromatographic, Fluorescence and Molecular Docking Study

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