Assessing the binding mode of ligands to DNA by time resolved fluorescence

摘要

Being able to determine the binding mode of a ligand to DNA, typically base intercalation (BI) or minor groove binding (MGB), is critical to determine the ligand therapeutic effects. Still, drug designers can only gain such information by means of indirect, complicated and very expensive methods [1]. We optimized a time resolved fluorescence excitation/detection setup [2] based on the use of picosecond lasers and non-commercial single photon avalanche diodes, which is endowed with 30 ps FWHM pulse response, high quantum efficiency and suitable time stability against electronic drifts. By fluorescence lifetime analysis, we revealed conformational changes induced in properly labelled DNA samples by the ligand-binding on an angstrom scale.