DNA-binding of water-soluble furocoumarins: a thermodynamic and conformational approach to understanding different biological effects.
The interaction of two water-soluble furocoumarins, 8-(omega-diethyl aminopropyloxy)psoralen hydrochloride (I) and its 5-isomer (II), with DNA has been investigated by spectroscopic, equilibrium dialysis, hydrodynamic and chiroptical techniques. Both compounds intercalate into the polynucleotide double helix. From the dependence of the binding on ionic strength, ion release and binding free energy corrected for counterion release have been quantitatively estimated. It is shown that the differences in DNA-affinity observed for compounds I and II arise primarily from non electrostatic contributions. The binding process is exothermic, with slightly different van't Hoff enthalpies for the examined furocoumarins. Helix lengthening and dichroic effects indicate different intercalation geometries for the isomeric compounds. These studies allow a possible explanation for the finding that isomer I exhibits largely better DNA-photobinding properties, while isomer II is by far more effective as an antiviral agent.
D000818:Animals; D002417:Cattle; D004247:DNA; D011564:Furocoumarins; D007700:Kinetics; D009690:Nucleic Acid Conformation; D012995:Solubility; D013816:Thermodynamics; D013950:Thymus Gland
D011564:Furocoumarins; C043665:5-(3-diethylaminopropoxy)psoralen; C043664:8-(3-diethylaminopropoxy)psoralen; D004247:DNA