Molecular aspects on the interaction of sanguinarine with B-form, Z-form and HL-form DNA structures.
The interaction of sanguinarine with right-handed (B-form), left-handed (Z-form) and left-handed (HL-form) structures of poly(dG-dC).poly(dG-dC) has been investigated by measuring the circular dichroism (CD) and UV-absorption spectral analysis. Sanguinarine binds strongly to the B-form DNA and does not bind to Z-form or HL-form, but it converts the Z-form and the HL-form back to the bound right handed form as evidenced from CD spectroscopy. Sanguinarine inhibits the rate of B to Z transition under ionic conditions that otherwise favour the left-handed conformation of the polynucleotides. UV absorption kinetic studies show that the Z-form reverses back to B-form to B-form on binding to sanguinarine. Binding isotherms obtained from spectrophotometric data show that sanguinarine binds strongly to the B-form polymer in a non-cooperative manner, in sharp contrast to the highly cooperative interaction under Z-form and HL-form polynucleotides. These studies reveal that the alternating GC sequence undergoes defined conformational changes and interacts with sanguinarine which may be an important aspect in understanding its extensive biological activities.
Maiti
M
M
Biophysical Chemistry Laboratory, Indian Institute of Chemical Biology, Calcutta 700 032, India. mmati@iicb.res.in
D000470:Alkaloids / Q000494:pharmacology*; D053119:Benzophenanthridines; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry*; D006859:Hydrogen / Q000737:chemistry*; D006860:Hydrogen Bonding; D007364:Intercalating Agents / Q000494:pharmacology*; D007546:Isoquinolines; D007700:Kinetics; D008956:Models, Chemical; D009690:Nucleic Acid Conformation; D013053:Spectrophotometry; D013997:Time Factors
D000470:Alkaloids; D053119:Benzophenanthridines; D007364:Intercalating Agents; D007546:Isoquinolines; C051802:triplex DNA; D006859:Hydrogen; D004247:DNA; C005705:sanguinarine