3ircular dichroism simulation shows a site-II-to-site-I displacement of human serum albumin-bound diclofenac by ibuprofen

Yamasaki, Keishi; Rahman, Mohammed Hablbur; Tsutsumi, Yasuhiro; Maruyama, Toru; Ahmed, Shamim; Kragh-Hansen,; Otagiri, Masaki

doi:10.1208/pt010212

Cited by 27 publications

(33 citation statements)

References 9 publications

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“…Drugs: Warfarin 1) 3.4ϫ10 5 10) Diazepam 1) 3.8ϫ10 5 48) Azapropazone 120) 2.8ϫ10 5 9) Ketoprofen 133) 2.5ϫ10 6 136) Phenylbutazone 1) 1.5ϫ10 6 10) Chlofibrate 1) 7.6ϫ10 5 137) Acenocoumarol 10) 2.2ϫ10 5 10) Iopanoate 1) 6.7ϫ10 6 131) Salicylate 1) 1.9ϫ10 5 9) Ibuprofen 22,68) 2.7ϫ10 6 21) Indomethacin 1) 1.4ϫ10 6 129) Pirprofen 72) 3.9ϫ10 5 72) Tolbutamide 1) 4.0ϫ10 4 130) S-Naproxen 1) 3.7ϫ10 6 89) Chlorpropamide 1) 3.3ϫ10 5 9) Ethacrynate 1) 1.7ϫ10 6 34) Iophenoxate 1) 7.7ϫ10 7 131) Chlorothiazide 134) 5.5ϫ10 4 134) Iodipamide 10) 9.9ϫ10 6 10) Diclofenac 76) 3.3ϫ10 6 76) Sulfadimethoxine 121) 9.0ϫ10 4 121) S(Ϫ)-Thiamylal 56) 8.7ϫ10 4 56) Sulfathiazole 9) 2.5ϫ10 4 9) S-Etodolac 59) 2.0ϫ10 5 59) Furosemide 122) 1.9ϫ10 5 122) Carprofen 75) Ͼ10 6 75) Tenoxicam 123) 3.7ϫ10 5 123) Suprofen 68) N.D. R-Sulbenicillin 111) 5.2ϫ10 3 111) Benoxaprofen 22) N.D. Valproate 60) 2.8ϫ10 5 60) Cicloprofen 22) N.D. Piretanide 122) 9.5ϫ10 4 122) Azidodeoxythymidine 15) N.D. Spironolactone …”

Section: Ligand Bindingunclassified

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Practical Aspects of the Ligand-Binding and Enzymatic Properties of Human Serum Albumin.

Kragh‐Hansen

Chuang

Otagiri

2002

Biological & Pharmaceutical Bulletin

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929

776

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Recent work with approaches like recombinant mutants and X-ray crystallography has given much new information about the ligand-binding properties of human serum albumin (HSA). The information increases the understanding of this unique transport and depot protein and could give a structural basis for the possible construction of therapeutic agents with altered HSA-binding properties. A tabulation of high-affinity binding sites for both endogenous and exogenous compounds has been made; it could be useful for the above-mentioned purpose, but it could also be of value when trying to predict potential drug interactions at the protein-binding level. Drug displacement is not always a complication to therapy; it can be used to increase the biological effect of a drug. However, due to rebinding at other sites, the increase in the free concentration of a displaced ligand can be less than expected. Drugs and drug metabolites can also interact covalently with HSA; thiol-containing drugs often bind to the single free cysteine residue of HSA, and glucuronidated drugs react irreversibly with other residues of the protein. Reversible binding of ligands is often stereospecific, and therefore immobilized HSA can be used to separate drug isomers. Albumin-containing dialysates are useful for extracorporeal removal of endogenous toxins and in the treatment of drug overdoses. HSA has different types of hydrolytic activities, which also can be stereospecific. The esterase-like property seems especially useful in converting prodrugs to active drugs in plasma.

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Section: Ligand Bindingunclassified

“…75) Such a site II-to-site I displacement has also been observed for diclofenac in the presence of ibuprofen. 76) …”

Section: -6 Rebinding After Displacementmentioning

confidence: 99%

Practical Aspects of the Ligand-Binding and Enzymatic Properties of Human Serum Albumin.

Kragh‐Hansen

Chuang

Otagiri

2002

Biological & Pharmaceutical Bulletin

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929

776

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“…A site II-to-site I displacement effect of ibuprofen was also found to be true for diclofenac. 33 Drug binding can be modulated by the simultaneous binding of endogenous compounds. Anions of long-chain fatty acids can, at low ligand-to-protein molar ratios (2:1), most probably allosterically, diminish the binding of S(2)and R(1)-thiamylal, diazepam, L-tryptophan, and dansylsarcosine to site II.…”

Section: Drug -Drug/endogeneous Compounds Interactionmentioning

confidence: 99%

Stereoselective binding of human serum albumin

2006

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Stereoselectivity in binding can have a significant effect on the drug disposition such as first-pass metabolism, metabolic clearance, renal clearance, and protein and tissue binding. Human serum albumin (HSA) is able to stereoselectively bind a great number of various endogenous and exogenous compounds. Various experimental data suggested that the two major drug-binding cavities, namely, site I and site II, do not seem to be the stereoselective binding sites of HSA. Stereoselective binding of HSA under disease conditions such as renal and hepatic diseases was found to be enhanced. In addition, site-to-site displacement of a site II-specific drug by another site II-specific drug was found to be stereoselective, too. Endogenous compounds such as long-chain fatty acids and uremic toxins are likely to cause combined direct and cascade effects that contribute to the preferential binding of a particular drug enantiomer. Taking together the findings of other studies, it is highly possible that the stereoselective binding site exists at the interface of the subdomains.

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“…The displacement of a drug from its binding site on HSA by other drugs or endogenous substances including fatty acids have also been reported to produce a sideto-side effect and an allosteric effect (9)(10)(11)(12). In addition, HSA may exist in different conformations at different pH, the N-F transition between pH 5.0 and 3.5, the F-E transition or acid expansion below pH 3.5, and the N-B transition between pH 7.0 and 9.0.…”

Section: Introductionmentioning

confidence: 99%

Histidine146 of human serum albumin plays a prominent role at the interface of subdomains IA and IIA in allosteric ligand binding

Kaneko¹,

Chuang²,

Minomo³

et al. 2011

IUBMB Life

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SummaryFatty acids are endogenous ligands of human serum albumin (HSA) that induce conformational changes and participate in allosteric ligand binding to HSA. In a previous study, we showed that, when myristate (MYR) is present, the binding of [ 14 C]ketoprofen (KP) to subdomain IA of HSA was increased, indicating that, when MYR binds to HSA, a new binding site in formed in that region. Meanwhile, an N-B transition has been reported to increase the binding of ligands at alkaline pH when the status of albumin is the B-conformer. Six histidine single mutants of HSA, H9A, H39A, H67A, H105A, H128A and H146A were produced and photolabeled with [ 14 C]KP at pH 6.5, 7.4 and 8.2 and the role of each histidine in causing the N-B transition induced allosteric ligand binding was examined. Cyanogen bromide cleavage of the photolabeled native HSA showed that subdomain IA was the site of the allosteric binding of KP at pH 8.2. From the photolabeling results, H146 was found to play a prominent role whilst H128 played little or no role in the allosteric binding. However, the remaining 4 mutants did not show a clear photolabeling pattern that was similar to either native HSA or H146A and, as a result, no firm conclusions can be made. An additional histidine mutant, H146I, was produced to confirm the results for H146A. A similar experiment using H146I showed that a benzene ring-like structure at position 146 is required for the allosteric ligand binding to occur.

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3ircular dichroism simulation shows a site-II-to-site-I displacement of human serum albumin-bound diclofenac by ibuprofen

Abstract: We have confirmed the existence of a site II-to-site I displacement, which is very striking and pharmacologically important, because the concentration of unbound drug being displaced is much lower than expected for a competitive mechanism.

Cited by 27 publications

References 9 publications

Practical Aspects of the Ligand-Binding and Enzymatic Properties of Human Serum Albumin.

Practical Aspects of the Ligand-Binding and Enzymatic Properties of Human Serum Albumin.

Stereoselective binding of human serum albumin

Histidine146 of human serum albumin plays a prominent role at the interface of subdomains IA and IIA in allosteric ligand binding

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