Influence of Palmitate and Oleate on the Binding of Warfarin to Human Serum Albumin: Stopped-Flow Studies

Rietbrock, N.; Menke, G; Reuter, G.; Laßmann, A.; Schmeidl, R.

doi:10.1515/cclm.1985.23.11.719

Cited by 13 publications

(11 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…29 In stopped-flow studies the fatty acid-induced binding of rac-warfarin manifested itself in an increased k 2 . 26 It is notable that defatted HSA was found to have increased susceptibility to drug-induced conformational changes. 30 The results presented in this work are in accordance with these findings.…”

Section: Discussionmentioning

confidence: 99%

Stereoselective kinetics of warfarin binding to human serum albumin: Effect of an allosteric interaction

2002

View full text Add to dashboard Cite

Kinetic and equilibrium binding studies were performed on the interaction of warfarin enantiomers with human serum albumin (HSA) in the absence and presence of lorazepam acetate (LoAc) enantiomers. Binding kinetics were followed by recording changes in the fluorescence of warfarin upon binding to HSA using the stopped-flow technique. The binding of (R)-warfarin displayed an exponentially increasing fluorescence, satisfying the two-step mechanism reported previously for the racemate, i.e., a diffusion controlled pre-equilibrium is followed by a slower rearrangement of the complex. In the case of (S)-warfarin, the signal was biphasic: a fast fluorescence enhancement was followed by a slow decline. The different kinetic features indicate that the equilibrium conformations of the [(S)-warfarin-HSA] and [(R)-warfarin-HSA] complexes are achieved via different mechanisms. The phenomenon was seen in buffers of different pH and compositions. Equilibrium binding measurements indicated significantly lower molar intrinsic fluorescence for the (S)-warfarin complex, suggesting differences in the microenvironments of the bound enantiomers. In the presence of (S)-LoAc, the allosterically enhanced binding of (S)-warfarin manifested itself in accelerated relaxation kinetics. In accordance with the low molar intrinsic fluorescence determined for the stable ternary complex, the amplitude of the decline in fluorescence became larger.

show abstract

Section: Discussionmentioning

confidence: 99%

Stereoselective kinetics of warfarin binding to human serum albumin: Effect of an allosteric interaction

2002

View full text Add to dashboard Cite

show abstract

“…Addition of up to three moles of long-chain FAs enhances the binding of Sudlow's site I (i.e., FA7) ligands. Although the reason for the enhancement of binding is not completely clear, it might be argued that a remarkable expansion of the site cavity and reorientation of Tyr150 residue could be at the basis of the observed behaviour (11,26,37,49,50). On the other hand, myristate bound at the heme site was suggested to be functionally linked to Sudlow's site I (26).…”

Section: Allosteric Modulation Of Drug Binding To Hsamentioning

confidence: 96%

The extraordinary ligand binding properties of human serum albumin

Fasano

Curry

Terreno

et al. 2005

IUBMB Life (International Union of Biochemistry and Molecular B

963

795

View full text Add to dashboard Cite

SummaryHuman serum albumin (HSA), the most prominent protein in plasma, binds different classes of ligands at multiple sites. HSA provides a depot for many compounds, affects pharmacokinetics of many drugs, holds some ligands in a strained orientation providing their metabolic modification, renders potential toxins harmless transporting them to disposal sites, accounts for most of the antioxidant capacity of human serum, and acts as a NO-carrier. The globular domain structural organization of monomeric HSA is at the root of its allosteric properties which are reminiscent of those of multimeric proteins. Here, structural, functional, biotechnological, and biomedical aspects of ligand binding to HSA are summarized. IUBMB Life, 57: 787 -796, 2005

show abstract

“…On the other hand, in the myristate-HSA-heme ternary complex the conformation of subdomain IIB is more similar to the conformation of ligand-free HSA rather than that of the myristate-HSA complex, either in the absence or presence of warfarin. Moreover, the long α-helix that connects subdomain IIB to IIIA is remarkably tilted, thus affecting both geometry and stereoselectivity of Sudlow's site II [3,23,[25][26][27][29][30][31]49,[57][58][59].…”

Section: Allosteric Modulation Of Drug Binding To Hsamentioning

confidence: 99%

Allosteric Modulation of Drug Binding to Human Serum Albumin

Ascenzi¹,

Bocedi²,

Notari³

et al. 2006

MRMC

164

180

View full text Add to dashboard Cite

Human serum albumin (HSA), the most prominent protein in plasma, is best known for its extraordinary ligand binding capacity. The three homologous domains of HSA (labeled I, II, and III), each in turn composed of two subdomains (named A and B), give rise to the three-dimensional structure of HSA. This flexible structural organization allows the protein structure to adapt to a variety of ligands. As conformational adaptability of HSA extends well beyond the immediate vicinity of the binding site(s), cooperativity and allosteric modulation arise among binding sites; this makes HSA similar to a multimeric protein. Although kinetic and thermodynamic parameters for ligand binding to HSA calculated by quantitative structure-activity relationship models are in excellent agreement with those obtained in vitro, cooperative and allosteric equilibria between different binding sites and competition between drugs or between drugs and endogenous ligands make difficult the interpretation of HSA binding properties in vivo. Binding of exogenous and endogenous ligands to HSA appears to be relevant in drug therapy and management. Here, the allosteric modulation of drug binding to HSA is briefly reviewed.

show abstract

Influence of Palmitate and Oleate on the Binding of Warfarin to Human Serum Albumin: Stopped-Flow Studies

Cited by 13 publications

References 20 publications

Stereoselective kinetics of warfarin binding to human serum albumin: Effect of an allosteric interaction

Stereoselective kinetics of warfarin binding to human serum albumin: Effect of an allosteric interaction

The extraordinary ligand binding properties of human serum albumin

Allosteric Modulation of Drug Binding to Human Serum Albumin

Contact Info

Product

Resources

About