A comparative study on the interaction of acridine and synthetic bis-acridine with G-quadruplex structure.
DNA from the telomeres contains a stretch of simple tandemly repeated sequences in which clusters of G residues alternate with clusters of T/A sequences along one DNA strand. Model telomeric G-clusters form four-stranded structures in presence of Na(I), K(I) and NH(4)(I) ions. Electrophoretic and spectroscopic studies were made with the telomeric related sequences d(T6G16) or d(G4T2G4T2G4T2G4). It was noticed earlier that G-quadruplex may either be inter-molecular, or intra-molecular, or a mixture of both. CD spectral characteristics of various G-quadruplex DNA suggests that the CD maximum at 293 nm corresponds to that of an intra-molecular G-quadruplex structure or hairpin dimers. Fluorescence titration studies also show that acridine and the bis-acridine are interacting with G-quadruplex DNA and destabilize the K(I)-quadruplex structure more efficiently than the quadruplex formed by NH(4)(I) ion. Among the two drugs studied, acridine is more capable of breaking the G-quadruplex structure than bis-acridine. This result is further confirmed by the CD experiments.
Nagesh
Narayana
N
Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500 007 (A.P), India. nagesh@ccmb.res.in
Krishnaiah
Abburi
A
D000166:Acridines / Q000138:chemical synthesis / Q000737:chemistry*; D000818:Animals; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry*; D019281:Dimerization; D015195:Drug Design; D004591:Electrophoresis, Polyacrylamide Gel; D054856:G-Quadruplexes; D015394:Molecular Structure; D009690:Nucleic Acid Conformation; D013050:Spectrometry, Fluorescence
D000166:Acridines; C484811:bis-acridine; D004247:DNA