SPECTROSCOPIC DETERMINATION OF BINDING INTERACTIONS OF ANTIVIRAL DRUG VALGANCICLOVIR WITH HS DNA

摘要

Studies on molecular interactions between drug and DNA are attracting the researchers all over the globe. Due to its well-established three dimensional structure and ease of prediction of its functional groups, DNA is largely preferred as an antiviral drug target. Valganciclovir (VGC) is an anti-cytomegalovirus drug with highly potent pharmacological and biological activities. The interaction of valganciclovir with herring sperm (hs) DNA was studied at physiological conditions by using various biophysical techniques. Formation of complex between VGC and hs DNA was confirmed by UV absorption and fluorescence spectroscopy analysis. Ethidium bromide (EB) was used as fluorescence probe as the intrinsic fluorescence of DNA is very low. The binding constant (K) value obtained was 0.70 x 104 LM1 for the formation of VGC-EB-hs-DNA complex. Negative values of enthalpy change (AH0) and entropy change (AS0) suggested the strong hydrogen bonding involved in the interaction between the drug and hs DNA. Conformational changes of hs DNA in presence of VGC were studied using circular dichroism (CD) and DNA melting analysis. Results confirm the minor groove binding mode of VGC which was concretely supported by viscosity and competitive displacement assay study using Hoechst 33258. Sequence specificity experiments determined the binding of VGC to A-T rich region of hs DNA.