Binding of the Anticancer Alkaloid Sanguinarine to double stranded RNAs: Insights into the Structural and Energetics Aspectsw.
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
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Title |
Binding of the Anticancer Alkaloid Sanguinarine to double stranded RNAs: Insights into the Structural and Energetics Aspectsw.
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Creator |
Roy Chowdhury,, Sebanti
Islamz, Md.Maidul Kumar, G Suresh |
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Subject |
Chemistry
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Description |
Elucidation of the molecular aspects of small molecule-RNA complexation is of prime importance
for rational RNA targeted drug design strategies. Towards this, the interaction of the cytotoxic
plant alkaloid sanguinarine to three double stranded ribonucleic acids, poly (A).poly(U),
poly(I).poly(C) and poly(C).poly(G) was studied using various biophysical and thermodynamic
techniques. Absorbance and fluorescence studies showed that the alkaloid bound cooperatively
to these RNAs with binding affinities of the order 104 M�1. Fluorescence quenching and
hydrodynamic studies gave evidence for intercalation of sanguinarine to these RNA duplexes.
Isothermal titration calorimetric studies revealed that the binding was characterized by negative
enthalpy and positive entropy changes and the affinity constants derived were in agreement with
the overall binding affinity values obtained from spectroscopic data. The binding of sanguinarine
stabilized the melting of poly(A). poly(U) and poly(I).poly(C) and the binding data evaluated
from the melting data were in agreement with that obtained from other techniques. The overall
binding affinity of sanguinarine to these double stranded RNAs varied in the order,
poly(A).poly(U) 4 poly(I).poly(C) c poly(C).poly(G). The temperature dependence of the
enthalpy changes afforded negative values of heat capacity changes for the binding of
sanguinarine to poly(A).poly(U) and poly(I).poly(C), suggesting substantial hydrophobic
contribution in the binding process. Further, enthalpy-entropy compensation phenomena was
also seen in poly(A).poly(U) and poly(I).poly(C) systems that correlated to the strong binding
involving a multiplicity of weak noncovalent interactions compared to the weak binding with
poly(C).poly(G). These results further advance our understanding on the binding of small
molecules that are specific binders to double stranded RNA sequences.
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Date |
2010
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Type |
Article
PeerReviewed |
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Format |
application/pdf
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Identifier |
http://www.eprints.iicb.res.in/46/1/MOLECULAR_BIOSYSTEMS__Volume_6___Issue_7;2010[132].pdf
Roy Chowdhury,, Sebanti and Islamz, Md.Maidul and Kumar, G Suresh (2010) Binding of the Anticancer Alkaloid Sanguinarine to double stranded RNAs: Insights into the Structural and Energetics Aspectsw. Molecular Biosystems, 6 (7). pp. 1265-1276. |
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Relation |
htpp://dx.doi.org/10.1039/b927001a
http://www.eprints.iicb.res.in/46/ |
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