Nucleic Acids Research Advance Access published online on July 28, 2008
Nucleic Acids Research, doi:10.1093/nar/gkn487
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Methods Online |
Mix and measure fluorescence screening for selective quadruplex binders
Chemistry Department, Wesleyan University, Middletown, CT 06459, USA
*To whom correspondence should be addressed. Tel: +1 860 685 2668; Fax: +1 860 685 2211; Email: pbolton{at}wesleyan.edu
Received May 14, 2008. Revised July 16, 2008. Accepted July 16, 2008.
The human genome contains thousands of regions, including that of the telomere, that have the potential to form quadruplex structures. Many of these regions are potential targets for therapeutic intervention. There are many different folding patterns for quadruplex DNAs and the loops exhibit much more variation than do the quartets. The successful targeting of a particular quadruplex structure requires distinguishing that structure from all of the other quadruplex structures that may be present. A mix and measure fluorescent screening method has been developed, that utilizes multiple reporter molecules that bind to different features of quadruplex DNA. The reporter molecules are used in combination with DNAs that have a variety of quadruplex structures. The screening is based on observing the increase or decrease in the fluorescence of the reporter molecules. The selectivity of a set of test molecules has been determined by this approach.