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Selective Binding of Distamycin A Derivative to G-Quadruplex Structure [d(TGGGGT)](4)
- Source :
- Journal of Nucleic Acids, Journal of Nucleic Acids, Vol 2010 (2010)
- Publication Year :
- 2010
-
Abstract
- Guanine-rich nucleic acid sequences can adopt G-quadruplex structures stabilized by layers of four Hoogsteen-paired guanine residues. Quadruplex-prone sequences are found in many regions of human genome and in the telomeres of all eukaryotic organisms. Since small molecules that target G-quadruplexes have been found to be effective telomerase inhibitors, the identification of new specific ligands for G-quadruplexes is emerging as a promising approach to develop new anticancer drugs. Distamycin A is known to bind to AT-rich sequences of duplex DNA, but it has recently been shown to interact also with G-quadruplexes. Here, isothermal titration calorimetry (ITC) and NMR techniques have been employed to characterize the interaction between a dicationic derivative of distamycin A (compound1) and the [d(TGGGGT)]4quadruplex. Additionally, to compare the binding behaviour of netropsin and compound1to the same target, a calometric study of the interaction between netropsin and [d(TGGGGT)]4has been performed. Experiments show that netropsin and compound1are able to bind to [d(TGGGGT)]4with good affinity and comparable thermodynamic profiles. In both cases the interactions are entropically driven processes with a small favourable enthalpic contribution. Interestingly, the structural modifications of compound1decrease the affinity of the ligand toward the duplex, enhancing the selectivity.
- Subjects :
- lcsh:QH426-470
Article Subject
Guanine
Stereochemistry
netropsin
Biology
Bioinformatics
G-quadruplex
Biochemistry
lcsh:Biochemistry
chemistry.chemical_compound
lcsh:QD415-436
heterocyclic compounds
Molecular Biology
Ligand
duplex
Isothermal titration calorimetry
Small molecule
NMR
isothermal titration calorimetry
lcsh:Genetics
chemistry
Netropsin
Duplex (building)
Nucleic acid
Research Article
Subjects
Details
- ISSN :
- 2090021X
- Volume :
- 2010
- Database :
- OpenAIRE
- Journal :
- Journal of nucleic acids
- Accession number :
- edsair.doi.dedup.....f70550739c7f9a8c1070676ca2265c2e