ANIONIC PORPHYRIN MOLECULES TO G-QUADRUPLEXED DNA USING FLUORESCENTLY LABLED
Yossry Hussein,James S.Godde, Mary E.Hawkins and Lesley Davenport.
CUNY Graduate Center and Brooklyn College, 2900 Bedford Avenue, Brooklyn NY 11210
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.
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.