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Recognition of human telomeric G-quadruplex DNA by berberine analogs: effect of substitution at the 9 and 13 positions of the isoquinoline moiety

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Title Recognition of human telomeric G-quadruplex DNA by berberine analogs: effect of substitution at the 9 and 13 positions of the isoquinoline moiety
 
Creator Bhowmik, Debipreeta
Fiorillo, Gaetano
Lombardi, Paolo
Kumar, G Suresh
 
Subject Chemistry
 
Description G-quadruplex forming sequences are widely distributed in human genome and serve as novel targets for regulating
gene expression and chromosomal maintenance. They offer unique targets for anticancer drug development. Here,
the interaction of berberine (BC) and two of its analogs bearing substitution at 9 and 13-position with human
telomeric G-quadruplex DNA sequence has been investigated by biophysical techniques. Both the analogs exhibited
several-fold higher binding affinity than berberine. The Scatchard binding isotherms revealed non-cooperative
binding. 9-ω-amino hexyl ether analog (BC1) showed highest affinity (1.8 × 106M�1) while the affinity of the 13-
phenylpropyl analog (BC2) was 1.09 × 106M�1. Comparative fluorescence quenching and polarization anisotropy
of the emission spectra gave evidence for a stronger stacking interaction of the analogs compared to berberine.
The thiazole orange displacement assay has clearly established that the analogs were more effective in displacing the end stacked dye in comparison to berberine. However, the binding of the analogs did not induce any major
structural perturbation in the G-quadruplex structure, but led to higher thermal stability. Energetics of the binding
indicated that the association of the analogs was exothermic and predominantly entropy driven phenomenon. Increasing the temperature resulted in weaker binding; the enthalpic contribution increased and the entropic contribution decreased. A small negative heat capacity change with significant enthalpy–entropy compensation
established the involvement of multiple weak noncovalent interactions in the binding process. The 9-ω-amino hexyl
ether analog stabilized the G-quadruplex structure better than the 13-phenyl alkyl analog.
 
Publisher John Wiley & Sons
 
Date 2015
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/2450/1/JOURNAL_OF_MOLECULAR_RECOGNITION__Vol._28__(_12_)722%2D730_;2015.pdf
Bhowmik, Debipreeta and Fiorillo, Gaetano and Lombardi, Paolo and Kumar, G Suresh (2015) Recognition of human telomeric G-quadruplex DNA by berberine analogs: effect of substitution at the 9 and 13 positions of the isoquinoline moiety. Journal of Molecular Recognition, 28 (12). pp. 722-730. ISSN 0952-3499
 
Relation http://dx.doi.org/10.1002/jmr.2486
http://www.eprints.iicb.res.in/2450/