Quantitative studies of allosteric effects by biointeraction chromatography: analysis of protein binding for low-solubility drugs.

Analytical Chemistry
Jianzhong Chen, David S Hage

Abstract

A new chromatographic method was developed for characterizing allosteric interactions between an immobilized binding agent and low-solubility compounds. This approach was illustrated by using it to characterize the interactions between tamoxifen and warfarin during their binding to the protein human serum albumin (HSA), with beta-cyclodextrin being employed as a solubilizing agent for these drugs. It was confirmed in this work through several experiments that warfarin had a single binding site on HSA with an association equilibrium constant of (2-5) x 10(5) M(-1) (average, 3.9 x 10(5) M(-1)) at 37 degrees C, in agreement with previous reports. It was also found that tamoxifen had a single major binding site on HSA, with an association equilibrium constant of (3-4) x 10(7) M(-1) (average, 3.5 x 10(7) M(-1)) at 37 degrees C. When warfarin was used as a mobile-phase additive in competition studies with tamoxifen, this had a positive allosteric effect on tamoxifen/HSA binding, giving a coupling constant of 2.3 (+/-0.3). Competitive studies using tamoxifen as a mobile-phase additive indicated that tamoxifen had a negative allosteric effect on warfarin/HSA binding, providing a coupling constant of 0.79 (+/-0.03). A unique feature of ...Continue Reading

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Citations

Feb 28, 2014·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Xiwei ZhengDavid S Hage
Jul 16, 2013·Acta Pharmacologica Sinica·Qi ShenSu Zeng
Oct 22, 2009·The Annals of Pharmacotherapy·Carrie B GivensAndrea S Franks
Apr 29, 2015·Analytical and Bioanalytical Chemistry·Ryan MatsudaDavid S Hage
Jul 1, 2011·Analytical Methods : Advancing Methods and Applications·David S HageXiwei Zheng
Mar 28, 2017·Separations·Cong BiDavid S Hage
Apr 30, 2017·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·James M KellyJohn W Babich
Feb 7, 2012·Journal of Pharmaceutical and Biomedical Analysis·David S HageXiwei Zheng

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