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Structural and thermodynamic basis of interaction of the putative anticancer agent chelerythrine with single, double and triple-stranded RNAs

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Title Structural and thermodynamic basis of interaction
of the putative anticancer agent chelerythrine with
single, double and triple-stranded RNAs
 
Creator Basu, Pritha
Kumar, Gopinatha Suresh
 
Subject Chemistry
 
Description comparative study on the interaction of the natural plant alkaloid chelerythrine with triple helical poly(U)$
poly(A)*poly(U), double helical poly(A)$poly(U) and single stranded poly(U) (the dot and star representing the
Watson-Crick and Hoogsteen base pairing) has been performed using various biophysical and thermodynamic techniques. Chelerythrine binds to the duplex and triplexes in a cooperative manner with affinity of the order of 106 M�1. A weaker binding (�105 M�1) in a non-cooperative mode occurred
with poly(U). Chelerythrine is more selective towards RNA triplex than its parent duplex. The triplex was stabilized specifically without affecting the stability of the duplex. Fluorescence quenching, fluorescence polarization and energy transfer from the nucleotides to the alkaloid, and viscosity results gave convincing evidence for a true intercalative binding of chelerythrine to the triplex and the duplex structures, and partial base stacking with poly(U). The conformations of both double and triple helices
were perturbed on binding but no effect occurred to the single strand structure. The binding of the alkaloid to all three RNA helices was found to be exothermic; to the triplex it was entropy driven with favorable enthalpy change, to the duplex enthalpy driven and to the single strand it was enthalpy driven.These results provide new knowledge on the mode, mechanism and specificity, and energetics of binding of the natural alkaloid and putative anticancer agent chelerythrine to different RNA conformations
 
Date 2015
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/2691/1/RSC_Adv.%2C_2015%2C_5%2C_29953%E2%80%9329964.pdf
Basu, Pritha and Kumar, Gopinatha Suresh (2015) Structural and thermodynamic basis of interaction of the putative anticancer agent chelerythrine with single, double and triple-stranded RNAs. Royal Society of Chemistry Advances, 5. pp. 29953-29964.
 
Relation http://www.eprints.iicb.res.in/2691/