Characterization of the interaction of the radioprotector 1-methyl-2-[2-(methylthio)-2-piperidinovinyl]quinolinium iodide with supercoiled DNA.
The interaction of the radioprotector 1-methyl-2-[2-(methylthio)-2-piperidinovinyl]quinolinium iodide (VQ) with linear and supercoiled pIBI30 DNA was studied by flow linear dichroism spectroscopy, equilibrium dialysis, circular dichroism, and UV absorption spectroscopy. The negative linear dichroism spectra of VQ-DNA complexes throughout the 220-500 nm wavelength region, a red shift in the VQ main absorption band (at 452 nm) of 1-2 nm upon binding to DNA, and a concentration-dependent unwinding of supercoiled DNA suggest that the primary mode of interaction of VQ with DNA (at least at low concentrations) is intercalative in nature. A least-squares analysis of the equilibrium dialysis binding of VQ to supercoiled DNA using the McGhee-von Hippel equation gives an association constant K = 7300 +/- 300 M-1, and an exclusion number n in the range of 3.3-5.3. The lower value of n is obtained when effects of polyelectrolytes are also taken into account. Because quinolinium iodide derivatives with different substituents and DNA binding affinities can be synthesized, this family of compounds could be employed to probe relationships, if any, between radioprotective efficacy and DNA binding affinity.
Swenberg
C E
CE
Radiation Biochemistry Department, Armed Forces Radiobiology Research Institute, Bethesda, Maryland 20889-5145.
Birke
S
S
Geacintov
N E
NE
D002942:Circular Dichroism; D004278:DNA, Superhelical / Q000378:metabolism*; D003956:Dialysis; D006358:Hot Temperature; D011806:Quinolinium Compounds / Q000378:metabolism*; D011837:Radiation-Protective Agents / Q000378:metabolism*
D004278:DNA, Superhelical; D011806:Quinolinium Compounds; D011837:Radiation-Protective Agents; C071510:1-methyl-2-(2-(methylthio)-2-piperidinovinyl)quinolinium