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Probing the Binding of two Sugar Bearing Anticancer Agents Aristololactam–b-D-Glucoside and Daunomycin to Double Stranded RNA Polynucleotides: a Combined Spectroscopic and Calorimetric study

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Title Probing the Binding of two Sugar Bearing Anticancer Agents
Aristololactam–b-D-Glucoside and Daunomycin to Double Stranded RNA Polynucleotides: a Combined Spectroscopic and Calorimetric study
 
Creator Das, Abhi
Kumar, G Suresh
 
Subject Chemistry
 
Description The plant alkaloid aristololactam–b-D-glucoside and the anticancer chemotherapy drug
daunomycin are two sugar bearing DNA binding antibiotics. The binding of these molecules to
three double stranded ribonucleic acids, poly(A)�poly(U), poly(I)�poly(C) and poly(C)�poly(G),
was studied using various biophysical techniques. Absorbance and fluorescence studies revealed
that these molecules bound non-cooperatively to these ds RNAs with the binding affinities of the
order 106 for daunomycin and 105 M�1 for aristololactam–b-D-glucoside. Fluorescence quenching
and viscosity studies gave evidence for intercalative binding. The binding enhanced the melting
temperature of poly(A)�poly(U) and poly(I)�poly(C) and the binding affinity values evaluated
from the melting data were in agreement with that obtained from other techniques. Circular
dichroism results suggested minor conformational perturbations of the RNA structures. The
binding was characterized by negative enthalpy and positive entropy changes and the affinity
constants derived from calorimetry were in agreement with that obtained from spectroscopic data.
Daunomycin bound all the three RNAs stronger than aristololactam–b-D-glucoside and the
binding affinity varied as poly(A)�poly(U) > poly(I)�poly(C) > poly(C)�poly(G). The temperature
dependence of the enthalpy changes yielded negative values of heat capacity changes for the
complexation suggesting substantial hydrophobic contribution to the binding process.
Furthermore, an enthalpy–entropy compensation behavior was also seen in all systems.
These results provide new insights into binding of these small molecule drugs to double
stranded RNA sequences.
 
Date 2012
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/1525/1/MOLECULAR_BIOSYSTEMS__8(_7)1958%2D1969;2912[64].pdf
Das, Abhi and Kumar, G Suresh (2012) Probing the Binding of two Sugar Bearing Anticancer Agents Aristololactam–b-D-Glucoside and Daunomycin to Double Stranded RNA Polynucleotides: a Combined Spectroscopic and Calorimetric study. Molecular BioSystems, 8 (7). pp. 1958-1969.
 
Relation http://dx.doi.org/10.1039/c2mb25080b
http://www.eprints.iicb.res.in/1525/