Journal article
Structure-activity relationships for the binding of polymyxins with human alpha-1-acid glycoprotein
Mohammad AK Azad, Johnny X Huang, Matthew A Cooper, Kade D Roberts, Philip E Thompson, Roger L Nation, Jian Li, Tony Velkov
BIOCHEMICAL PHARMACOLOGY | PERGAMON-ELSEVIER SCIENCE LTD | Published : 2012
Abstract
Here, for the first time, we have characterized binding properties of the polymyxin class of antibiotics for human α-1-acid glycoprotein (AGP) using a combination of biophysical techniques. The binding affinity of colistin, polymyxin B, polymyxin B(3), colistin methansulfonate, and colistin nona-peptide was determined by isothermal titration calorimetry (ITC), surface plasma resonance (SPR) and fluorometric assay methods. All assay techniques indicated colistin, polymyxin B and polymyxin B(3) display a moderate binding affinity for AGP. ITC and SPR showed there was no detectable binding affinity for colistin methansulfonate and colistin nona-peptide, suggesting both the positive charges of t..
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Awarded by National Institute of Allergy and Infectious Diseases of the National Institutes of Health
Awarded by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
Funding Acknowledgements
T.V., R.L.N., J.L., P.E.T. and K.R. are supported by the Australian National Health and Medical Research Council (NHMRC). 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 R01A1079330). 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. M.C. is an NHMRC Australia Fellow. J.L. is an Australian NHMRC Senior Research Fellow. T.V. is an Australian NHMRC Industry Career Development Research Fellow.