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Published abstracts of research posters presented at the 47th Annual Meeting of the Biophysical Society in Boston, February 2003


 

BINDING OF ANIONIC PORPHYRIN MOLECULES TO G-QUADRUPLEXED DNA USING FLUORESCENTLY LABLED GUANINE-TELOMERIC SEQUENCES.

Yossry Hussein,James S.Godde, Mary E.Hawkins and Lesley Davenport. CUNY Graduate Center and Brooklyn College, 2900 Bedford Avenue, Brooklyn NY 11210
Monmouth College, 700 East Broadway, Monmouth, Illinois 61462
NCI/NIH, CenterDrive, Bethesda, Maryland 20892


Human telomeres contain many repeats of the guanine-rich hexamer (TTAGGG)n. The oligonucleotide (TTAGGG)4 forms G-quadruplex structures in the presence of physiological concentrations of K+. We are investigating G-quadruplex stabilizing agents that exhibit high binding affinity and selectivity for the DNA-quadruplex as potential chemotherapy agents. Interactions of the anionic porphyrins NMM and Co(III)MPIX have been explored by selective replacement of the 5th or 11th guanine residues of (TTAGGG)4 with a fluorescent pteridine derivative, 6MI. Melting profiles and electrophoresis gels confirm tetrad formation, with a decrease in fluorescence intensity observed for the 5-6MI sequence and an enhancement for 11-6MI, suggesting sensitivity of the signal to local environment and DNA conformation. Both labeled oligonucleotides exhibit fluorescence quenching and tight binding with addition of Co(III)MPIX (Ka~107 mol-1) and NMM (Ka~106 mol-1). Additionally, enhancement of porphyrin fluorescence for NMM, and dialysis studies for Co(III)MPIX suggests that these anionic porphyrins exhibit high selectivity for quadruplex-DNA over ssDNA and dsDNA.

 

 Hussein,Y.,James S.Godde, Mary E.Hawkins and Davenport, L. (2003) ' Binding of Anionic Porphyrin Molecules to G-Quadruplexed DNA Using Fluorescently Labeled Guanine-Telomeric Sequences.', Biophysical J., Submitted.