Molecular Recognition of DNA by Small Molecules: AT Base Pair Specific Intercalative Binding of Cytotoxic Plant Alkaloid Palmatine
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
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| Title |
Molecular Recognition of DNA by Small Molecules: AT Base Pair Specific Intercalative Binding of Cytotoxic Plant Alkaloid Palmatine
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| Creator |
Bhadra, Kakali
Maiti, Motilal Kumar, G Suresh |
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| Subject |
Chemistry
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| 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.
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| Date |
2007
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| Type |
Article
PeerReviewed |
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| Format |
application/pdf
application/pdf |
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| Identifier |
http://www.eprints.iicb.res.in/1093/1/BIOCHIMICA_ET_BIOPHYSICA_ACTA%2DGENERAL_SUBJECTS__1770_(_7_)1071%2D1080_;2007[69].pdf
http://www.eprints.iicb.res.in/1093/2/BIOCHIMICA_ET_BIOPHYSICA_ACTA%2DGENERAL_SUBJECTS__1770_(_7_)1071%2D1080_;2007[69].pdf Bhadra, Kakali and Maiti, Motilal and Kumar, G Suresh (2007) Molecular Recognition of DNA by Small Molecules: AT Base Pair Specific Intercalative Binding of Cytotoxic Plant Alkaloid Palmatine. BBA - Biochimica et Biophysica Acta, 1770 (7). pp. 1071-1080. |
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| Relation |
http://dx.doi.org/10.1016/j.bbagen.2007.03.001
http://www.eprints.iicb.res.in/1093/ |
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