Molecular Recognition And Interaction Between Three Kinds Of β-Lactam Antibiotics And Bovine Serum Albumin

Objective:This study was designed to investigate the molecular recognition and interaction of bovine serum albumin (BSA) and three β-lactam antibiotics such as Penicillin G (PENG), Penicillin V (PENV) and Cefalexin (CEF) by fluorescence spectroscopy in combination with affinity chromatography and molecular docking under the simulated physiological conditions.Methods:The Stern-Volmer quenching constants (Ksv), binding constants (Ka), number of binding sites (n), and thermodynamic data of the binding reactions (△G,△H and△S) were obtained at different temperatures. The synchronous fluorescence spectra and Red edge excitation shift can give some information about the molecular environment in a vicinity of chromophoric molecules. Warfarin and ibuprofen were chosen as site probes to identify the binding site on BSA by antibiotics. Meanwhile, affinity chromatography and molecular docking were used as assistance methods.Results and Conclusion:These antibiotics inserted into the sub-domains ⅢA (site Ⅱ) of BSA mainly by Van der Waals force and hydrogen interaction, and significantly quenched its inner fluorescence through static quenching. A common result was authenticated that the combining abilities of the antibiotics to BSA molecule ranked in the order of CEF>PENV> PENG, which speculated that the interaction strength is closely related to structure of side chain and flexibility of molecule. Meanwhile, molecular docking was performed to reveal the possible binding mode and assess the microenvironment around the bound antibiotics, which were consistent with the results from the spectral experiments. This study could be a useful guideline for the clinical medication and new antibiotics design.