RNA Targeting by DNA Binding Drugs: Structural, Conformational and Energetic Aspects of the Binding of Quinacrine and DAPI toA-form and HL-form of poly(rC)·poly(rG)
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
View Archive Info| Field | Value | |
| Title |
RNA Targeting by DNA Binding Drugs: Structural, Conformational and Energetic Aspects of the Binding of Quinacrine and DAPI toA-form and HL-form of poly(rC)·poly(rG)
|
|
| Creator |
Sinha , Rangana Sinha
Hossain, Maidul Kumar, G Suresh |
|
| Subject |
Chemistry
|
|
| Description |
A key step in the rational design of new RNA binding small molecules necessitates a complete elucidation of the molecular aspects of the
binding of existing molecules to RNA structures. This work focuses towards the understanding of the interaction of a DNA intercalator, quinacrine
and a minor groove binder 4′,6-diamidino-2-phenylindole (DAPI) with the right handed Watson–Crick base paired A-form and the left-handed
Hoogsteen base paired HL-form of poly(rC)·poly(rG) evaluated by multifaceted spectroscopic and viscometric techniques. The energetics of their
interaction has also been elucidated by isothermal titration calorimetry. Results of this study converge to suggest that (i) quinacrine intercalates to
both A-form and HL-form of poly(rC)·poly(rG); (ii) DAPI shows both intercalative and groove-binding modes to the A-form of the RNA but
binds by intercalative mode to the HL-form. Isothermal calorimetric patterns of quinacrine binding to both the forms of RNA and of DAPI binding
to the HL-form are indicative of single binding while the binding of DAPI to the A-form reveals two kinds of binding. The binding of both the
drugs to both conformations of RNA is exothermic; while the binding of quinacrine to both conformations and DAPI to the A-form (first site) is
entropy driven, the binding of DAPI to the second site of A-form and HL-conformation is enthalpy driven. Temperature dependence of the binding
enthalpy revealed that the RNA–ligand interaction reactions are accompanied by small heat capacity changes that are nonetheless significant. We
conclude that the binding affinity characteristics and energetics of interaction of these DNA binding molecules to the RNA conformations are
significantly different and may serve as data for the development of effective structure selective RNA-based antiviral drugs.
© 2007 Elsevier B.V. All rights reserved.
|
|
| Publisher |
Elsevier
|
|
| Date |
2007
|
|
| Type |
Article
PeerReviewed |
|
| Format |
application/pdf
|
|
| Identifier |
http://www.eprints.iicb.res.in/1065/1/BIOCHIMICA_ET_BIOPHYSICA_ACTA%2DGENERAL_SUBJECTS__1770_(_7_)1071%2D1080_;2007[69].pdf
Sinha , Rangana Sinha and Hossain, Maidul and Kumar, G Suresh (2007) RNA Targeting by DNA Binding Drugs: Structural, Conformational and Energetic Aspects of the Binding of Quinacrine and DAPI toA-form and HL-form of poly(rC)·poly(rG). BBA - Biochimica et Biophysica Acta, 1770. pp. 1636-1650. |
|
| Relation |
http://dx.doi.org/10.1016/j.bbagen.2007.08.018
http://www.eprints.iicb.res.in/1065/ |
|