Molecular aspects on the interaction of sanguinarine with B-form, Z-form and H^L- form DNA structures

Abstract

The interaction of sanguinarine with right-handed (B-form), left-handed (Z- form) and left-handed (H^L- 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 H^L-form, but it converts the Z form and the H^L-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 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  H^L-form polynucleotides. These studies reveal that the alternating GC sequence undergoes defined conformation changes and interacts with singuinarine which may be an important aspect in understanding its extensive biological activities.