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Interactions of chromomycin A<sub>3</sub> and mithramycin with the sequence d(TAGCTAGCTA)<sub>2</sub>

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Title Interactions of chromomycin A3 and mithramycin with the sequence d(TAGCTAGCTA)2
 
Creator Chakrabarti, Sukanya
Dasgupta, Dipak
 
Description 64-70
Anti-cancer antibiotics, chromomycin A3
(CHR) and mithramycin (MTR) inhibit DNA directed RNA synthesis in vivo by
binding reversibly to template DNA in the minor groove with GC base
specificity, in the presence of divalent cations like Mg2+.
Under physiological conditions, (drug)2 Mg2+ complexes
formed by the antibiotics are the potential DNA binding ligands.
Structures of CHR and MTR differ in their saccharide residues. Scrutiny of the
DNA binding properties reveal significant differences in their sequence
selectivity, orientation and stoichiometry of binding. Here, we have analyzed
binding and thermodynamic parameters for the interaction of the antibiotics
with a model oligonucleotide sequence, d(TAGCTAGCTA)2 to
understand the role of sugars. The oligomer contains two potential binding
sites (GpC) for the ligands. The study illustrates that the drugs bind
differently to the sequence. (MTR)2Mg2+ binds to both
sites whereas (CHR)2Mg2+ binds to a single site.
UV melting profiles for the decanucleotide saturated with the ligands show that
MTR bound oligomer is highly stabilized and melts symmetrically. In
contrast, with CHR, loss of symmetry in the oligomer following its association
with a single (CHR)2Mg2+ complex molecule leads to a
biphasic melting curve. Results have been interpreted in the light of
saccharide dependent differences in ligand flexibility between the two
antibiotics.
 
Date 2013-07-16T06:05:22Z
2013-07-16T06:05:22Z
2001-04
 
Type Article
 
Identifier 0975-0959 (Online); 0301-1208 (Print)
http://hdl.handle.net/123456789/19800
 
Language en_US
 
Rights CC Attribution-Noncommercial-No Derivative Works 2.5 India
 
Publisher NISCAIR-CSIR, India
 
Source IJBB Vol.38(1-2) [February-April 2001]