The Plasma Protein Binding Proteome of Ertapenem: A Novel Compound-Centric Proteomic Approach for Elucidating Drug-Plasma Protein Binding Interactions
Mark A Baker, Elena K Schneider, Johnny X Huang, Matthew A Cooper, Jian Li, Tony Velkov
ACS CHEMICAL BIOLOGY | AMER CHEMICAL SOC | Published : 2016
Ertapenem is an important first-line carbapenem antibiotic used for the treatment of aerobic Gram-negative bacterial infections. It is the only marketed carbapenem that is highly bound to plasma proteins and displays a concentration-dependent and saturable plasma protein binding profile. To date, the plasma components responsible for sequestering ertapenems antibacterial activity remain uncharacterized. In the present study, we have employed an orthogonal, multiplatform approach, including novel compound-centric displacement proteomics and surface plasmon resonance to characterize the plasma protein binding proteome of ertapenem. In proof-of-concept, the capacity of physiological cocktails o..View full abstract
Awarded by Australian National Health and Medical Research Council
This work and T.V., J.L., M.A.B., and M.A.C. are supported by the Australian National Health and Medical Research Council (Grant 1064896). M.A.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.