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RNA targeting through binding of small molecules: Studies on t-RNA binding by the cytotoxic protoberberine alkaloid coralynew

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Title RNA targeting through binding of small molecules: Studies on t-RNA
binding by the cytotoxic protoberberine alkaloid coralynew
 
Creator Islam, Md. Maidul
Pandya, Prateek
Kumar, Surat
Kumar, G Suresh
 
Subject Chemistry
 
Description Interaction of the protoberberine alkaloid coralyne with t-RNAphe was investigated using various
biophysical techniques. Results of absorption and fluorescence studies revealed that the alkaloid
binds to t-RNA exhibiting positive cooperativity. Isothermal titration calorimetry results
suggested that the binding of the alkaloid was predominantly enthalpy driven with a smaller
favourable entropy term. A surprisingly large favourable component for non-electrostatic
contribution to the binding of coralyne to t-RNA was revealed from salt dependence data and the
dissection of the free energy. The alkaloid enhanced the thermal stability of t-RNA and the
binding affinity values obtained from optical thermal melting data was in agreement with that
from calorimetry. The heat capacity change of �125 cal mol�1 K�1 and the observed significant
enthalpy–entropy compensation phenomenon confirmed the involvement of multiple weak
noncovalent interactions. Circular dichroism studies provided evidence for significant perturbation
of the t-RNA structure with concomitant induction of optical activity in the bound achiral
alkaloid molecules. Binding isotherms generated from circular dichroic data confirmed the
cooperative binding mode of the alkaloid as deduced from spectroscopic data. Docking studies
provided further insights into the partially intercalated state of coralyne inside the t-RNA
structure. This study presents a complete binding and thermodynamic profile of coralyne
interaction to t-RNA.
 
Date 2009
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/244/1/MOLECULAR_BIOSYSTEMS%2C5(3)%2C_244%2D254%2C2009[125].pdf
Islam, Md. Maidul and Pandya, Prateek and Kumar, Surat and Kumar, G Suresh (2009) RNA targeting through binding of small molecules: Studies on t-RNA binding by the cytotoxic protoberberine alkaloid coralynew. Molecular BioSystems, 5 (3). pp. 244-254.
 
Relation http://dx.doi.org/10.1039/b816480k
http://www.eprints.iicb.res.in/244/