Flow microdialysis sampling-chemiluminescent detection coupled with molecular docking for the investigation of...

The investigation of the binding behavior between drug and DNA provides basic information for understanding pharmacological and toxicologic mechanisms of many drugs. Herein, a facile chemiluminescent (CL) method for investigating the binding behavior between salbutamol and calf thymus DNA (ct-DNA) was established by utilizing flow microdialysis sampling technique. In a reaction equilibrium solution of salbutamol and ct-DNA, free salbutamol was extracted by a microdialysis probe, and then injected into a flow-injection CL detection system to quantitate its concentration. The binding constants of salbutamol acquired by Klotz analysis and Scatchard analysis were 2.97 × 10⁴ M^-1and 2.99 × 10⁴ M^-1, respectively. Salbutamol showed one sort of binding site on ct-DNA. Meanwhile, the three-dimensional spatial structure of the binding mode was investigated by molecular docking. The results indicate that the binding mode of salbutamol to ct-DNA was groove binding. The hydrogen bonds were primary driving force for the direct recognition of salbutamol by ct-DNA. This proof-of-principle method paves a pathway to investigate the binding behavior between small-molecular drug and DNA, and provides a theoretical guidance for designing DNA-targeting drugs.