Limits...
Mix and measure fluorescence screening for selective quadruplex binders.

Paramasivan S, Bolton PH - Nucleic Acids Res. (2008)

Bottom Line: The successful targeting of a particular quadruplex structure requires distinguishing that structure from all of the other quadruplex structures that may be present.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.

View Article: PubMed Central - PubMed

Affiliation: Chemistry Department, Wesleyan University, Middletown, CT 06459, USA.

ABSTRACT
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.

Show MeSH
The structures of the six test molecules used in the screening are shown.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2553591&req=5

Figure 5: The structures of the six test molecules used in the screening are shown.

Mentions: To investigate the utility of this approach we have applied it to a select set of test molecules. A diverse set of test molecules was chosen and the structures are shown in Figure 5. N-hexanoyl-d-sphingosine is a potent apoptotic (48) and the other test molecules have all been previously investigated for their interactions with quadruplex DNA (49–53). This set of test molecules contains sugar, peptide, planar aromatic, aliphatic chains and a variety of other structural features. This set was chosen to allow preliminary examination of whether any of these structural features interfere with the screen.Figure 5.


Mix and measure fluorescence screening for selective quadruplex binders.

Paramasivan S, Bolton PH - Nucleic Acids Res. (2008)

The structures of the six test molecules used in the screening are shown.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2553591&req=5

Figure 5: The structures of the six test molecules used in the screening are shown.
Mentions: To investigate the utility of this approach we have applied it to a select set of test molecules. A diverse set of test molecules was chosen and the structures are shown in Figure 5. N-hexanoyl-d-sphingosine is a potent apoptotic (48) and the other test molecules have all been previously investigated for their interactions with quadruplex DNA (49–53). This set of test molecules contains sugar, peptide, planar aromatic, aliphatic chains and a variety of other structural features. This set was chosen to allow preliminary examination of whether any of these structural features interfere with the screen.Figure 5.

Bottom Line: The successful targeting of a particular quadruplex structure requires distinguishing that structure from all of the other quadruplex structures that may be present.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.

View Article: PubMed Central - PubMed

Affiliation: Chemistry Department, Wesleyan University, Middletown, CT 06459, USA.

ABSTRACT
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.

Show MeSH