Journal article

Drug-binding energetics of human alpha-1-acid glycoprotein assessed by isothermal titration calorimetry and molecular docking simulations

Johnny X Huang, Matthew A Cooper, Mark A Baker, Mohammad AK Azad, Roger L Nation, Jian Li, Tony Velkov

JOURNAL OF MOLECULAR RECOGNITION | WILEY | Published : 2012

Abstract

This study utilizes sensitive, modern isothermal titration calorimetric methods to characterize the microscopic thermodynamic parameters that drive the binding of basic drugs to α-1-acid glycoprotein (AGP) and thereby rationalize the thermodynamic data in relation to docking models and crystallographic structures of the drug-AGP complexes. The binding of basic compounds from the tricyclic antidepressant series, together with miaserine, chlorpromazine, disopyramide and cimetidine, all displayed an exothermically driven binding interaction with AGP. The impact of protonation/deprotonation events, ionic strength, temperature and the individual selectivity of the A and F1*S AGP variants on drug-..

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University of Melbourne Researchers

Grants

Awarded by National Institute of Allergy and Infectious Diseases of the National Institutes of Health


Awarded by NHMRC Australia


Awarded by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES


Funding Acknowledgements

R.L.N. and J.L. are supported by research grants from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (R01A1070896 and R01AI079330). T.V, R.L.N, J.L, P.E.T, M.A.B, and K.R are also supported by the Australian National Health and Medical Research Council (NHMRC). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Allergy and Infectious Diseases or the National Institutes of Health. J.L. is an Australian NHMRC Senior Research Fellow. T.V. and M.B. are Australian NHMRC Industry Career Development Research Fellows. M.C. is an NHMRC Australia Fellow supported by AF511105.