Interaction of Small Molecules with Double-Stranded RNA: Spectroscopic, Viscometric, and Calorimetric Study of Hoechst and Proflavine Binding to PolyCG Structures
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
View Archive Info| Field | Value | |
| Title |
Interaction of Small Molecules with Double-Stranded RNA:
Spectroscopic, Viscometric, and Calorimetric Study
of Hoechst and Proflavine Binding to PolyCG Structures
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| Creator |
Sinha, Rangana
Hossain, Maidul Kumar, G Suresh |
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| Subject |
Chemistry
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| Description |
Design and synthesis of new small molecules binding to double-stranded RNA necessitate complete understanding
of the molecular aspects of the binding of many existing molecules. Toward this goal, in this work we
evaluated the biophysical aspects of the interaction of a DNA intercalator (proflavine) and a minor groove
binder (hoechst 33258) with two polymorphic forms of polyCG, namely, the right-handed Watson-Crick
base paired A-form and the left-handed Hoogsteen base paired HL-form, by absorption, fluorescence, and
viscometry experiments. The energetics of the interaction of these molecules with the RNA structures has also
been elucidated by isothermal titration calorimetry (ITC). Results suggest that proflavine strongly intercalates in
both forms of polyCG, whereas hoechst shows mainly groove-binding modes. The binding of both drugs to both
forms of RNA resulted in significant conformational change to the RNA structure with the bound molecules
being placed in the chiral RNA helix. ITC profiles for both proflavine and hoechst show two binding sites.
Binding of proflavine to both forms of RNA is endothermic and entropy driven in the first site and exothermic
and enthalpy driven in the second site, whereas hoechst binding to both forms of RNA is exothermic and
enthalpy driven in the first site and endothermic and entropy driven in the second site. This study suggests that
the binding affinity characteristics and energetics of interaction of these DNA binding molecules with the RNA
conformations are significantly different and may serve as data for future development of effective structureselective
RNA-based drugs.
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| Publisher |
Mary Ann Liebert
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| Date |
2009
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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/151/1/DNA_AND_CELL_BIOLOGY%2C28(4)%2C__209%2D219%2C2009[86].pdf
Sinha, Rangana and Hossain, Maidul and Kumar, G Suresh (2009) Interaction of Small Molecules with Double-Stranded RNA: Spectroscopic, Viscometric, and Calorimetric Study of Hoechst and Proflavine Binding to PolyCG Structures. DNA and Cell Biology, 28 (4). pp. 209-219. |
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| Relation |
http://dx.doi.org/10.1089=dna.2008.0838
http://www.eprints.iicb.res.in/151/ |
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