Interaction of daunomycin antibiotic with human serum albumin: investigation by resonant mirror biosensor technique, fluorescence spectroscopy and molecular modeling methods.
Daunomycin (DM) is a clinically used antitumor anthracycline antibiotic, which is transported primarily by human serum albumin (HSA) in the blood. Binding characteristics are therefore of interest for both the pharmacokinetics and pharmacodynamics of DM. A new optical biosensor technique based on the resonant mirror was used to characterize interaction of DM with HSA at different temperatures and the affinity constants were obtained. The HSA-DM interaction is exothermic with having favorable enthalpy and entropy followed by the integrated van't Hoff equation analysis. Fluorescence studies showed that DM has an ability to quench the intrinsic fluorescence of HSA through a static quenching procedure according to the Stern-Volmer equation and DM displays a pH-dependent binding affinity to HSA. Molecular modeling calculations showed that the DM binds HSA to a non-classical drug binding site and further analysis of the binding site of DM within the HSA molecule suggested that hydrophobic contacts, hydrogen bond formation and electrostatic interactions account for the binding of DM.
Tang
Kai
K
Key Laboratory of MOE for Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China.
Qin
Yi-Min
YM
Lin
Ai-Hua
AH
Hu
Xing
X
Zou
Guo-Lin
GL
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D001665:Binding Sites; D015374:Biosensing Techniques; D003630:Daunorubicin / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D008024:Ligands; D008956:Models, Chemical; D008958:Models, Molecular; D010100:Oxygen / Q000737:chemistry; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012709:Serum Albumin / Q000737:chemistry / Q000187:drug effects*; D012984:Software; D013050:Spectrometry, Fluorescence / Q000379:methods*; D013696:Temperature; D013816:Thermodynamics; D013997:Time Factors; D014364:Tryptophan / Q000737:chemistry
D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic; D008024:Ligands; D012709:Serum Albumin; D014364:Tryptophan; D010100:Oxygen; D003630:Daunorubicin