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Molecular recognition of DNA by small molecules: AT base pair specific intercalative binding of cytotoxic plant alkaloid palmatine

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Title Molecular recognition of DNA by small molecules: AT base pair specific intercalative binding of cytotoxic plant alkaloid palmatine
 
Creator Bhadra, K
Maiti, M
Kumar, GS
 
Subject Biochemistry & Molecular Biology; Biophysics
 
Description The base dependent binding of the cytotoxic alkaloid palmatine to four synthetic polynucleotides, poly(dA).poly(dT), poly(dA-dT).poly (dA-dT), poly(dG).poly(dC) and poly(dG-dC).poly(dG-dC) was examined by competition dialysis, spectrophotometric, spectrofluorimetric, thermal melting, circular dichroic, viscometric and isothermal titration calorimetric (ITC) studies. Binding of the alkaloid to various polynucleotides was dependent upon sequences of base pairs. Binding data obtained from absorbance measurements according to neighbour exclusion model indicated that the intrinsic binding constants decreased in the order poly(dA).poly(dT) > poly(dA-dT).poly(dA-dT) > poly(dG-dC).poly(dG-dC) > poly(dG).poly(dC). This affinity was also revealed by the competition dialysis, increase of steady state fluorescence intensity, increase in fluorescence quantum yield, stabilization against thermal denaturation and perturbations in circular dichroic spectrum. Among the polynucleotides, poly(dA).poly(dT) showed positive cooperativity, at binding values lower than r = 0.05. Viscosity studies revealed that in the strong binding region, the increase of contour length of DNA depended strongly on the sequence of base pairs being higher for AT polymers and induction of unwinding-rewinding process of covalently closed superhelical DNA. Isothermal titration calorimetric data showed a single entropy driven binding event in the AT homo polymer while that with the hetero polymer involved two binding modes, an entropy driven strong binding followed by an enthalpy driven weak binding. These results unequivocally established that the alkaloid palmatine binds strongly to AT homo and hetero polymers by mechanism of intercalation. (c) 2007 Elsevier B.V. All rights reserved.
 
Publisher ELSEVIER SCIENCE BVAMSTERDAMPO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
 
Date 2011-09-20T12:12:36Z
2011-09-20T12:12:36Z
2007
 
Type Proceedings Paper
 
Identifier BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
0304-4165
http://hdl.handle.net/123456789/14336
 
Language English