Authors: H. Aki, M. Goto, M. Kai, and M. Yamamoto
View More View Less
Restricted access

Abstract  

A multiple-site competitive model has been developed to evaluate quantitatively the equilibrium competition of drugs that bind to multiple classes of binding sites on human serum albumin (HSA). The equations, which are based on the multiple-class binding site model, assume that competition exists at individual sites, that the binding parameters for drug or drug competitor pertain to individual sites, and also that the binding parameters for drug or competitor at any given site are independent of drug or competitor bound at other sites. For the drug-competitor pairs, ethacrynic acid (EA) -caproic acid (C6), -lauric acid (C12), and -palmitic acid (C16), the reaction heat of EA binding to HSA was measured in the absence and the presence of fatty acids at the molar ratio of 3:1 with HSA at pH 7.4 and 37°C by isothermal titration microcalorimetry. The calorimetric titration data induced by the presence of fatty acids were directly compaired to the computer simulation curves by the corresponding multiple-site competititve models, which were precedently calculated from binding parameters of EA and fatty acids. In the case of EA-C12 or -C16 competitive binding, EA binding at the first and the second classes of binding sites on HSA were instantaneously inhibited by C12 or C16, resulting that the binding constant of the first class of binding sites of EA were decreased and that the second class of binding sites on HSA entirely disappeared. In the competition between EA and C6, the first class of binding sites of EA was diminished by C6, resulting in the decrease of the binding constants and the number of binding sites in the first class of EA, whereas, the second class of binding sites was unaffected. The multiple-site competitive model assuming site-site competition could be directly comparable to the calorimetric data and be suitable to account for the competitive processes for drugs bound to the multiple-class of binding sites on HSA.

Manuscript Submission: HERE

  • Impact Factor (2019): 2.731
  • Scimago Journal Rank (2019): 0.415
  • SJR Hirsch-Index (2019): 87
  • SJR Quartile Score (2019): Q3 Condensed Matter Physics
  • SJR Quartile Score (2019): Q3 Physical and Theoretical Chemistry
  • Impact Factor (2018): 2.471
  • Scimago Journal Rank (2018): 0.634
  • SJR Hirsch-Index (2018): 78
  • SJR Quartile Score (2018): Q2 Condensed Matter Physics
  • SJR Quartile Score (2018): Q2 Physical and Theoretical Chemistry

For subscription options, please visit the website of Springer.

Journal of Thermal Analysis and Calorimetry
Language English
Size A4
Year of
Foundation
1969
Volumes
per Year
4
Issues
per Year
24
Founder Akadémiai Kiadó
Founder's
Address
H-1117 Budapest, Hungary 1516 Budapest, PO Box 245.
Publisher Akadémiai Kiadó
Springer Nature Switzerland AG
Publisher's
Address
H-1117 Budapest, Hungary 1516 Budapest, PO Box 245.
CH-6330 Cham, Switzerland Gewerbestrasse 11.
Responsible
Publisher
Chief Executive Officer, Akadémiai Kiadó
ISSN 1388-6150 (Print)
ISSN 1588-2926 (Online)