Molecular probes of DNA bulges: functional assay and spectroscopic analysis.
Bulged structures in DNA and RNA have been linked to biomolecular processes involved in numerous diseases, thus probes with affinity for these nucleic acid targets would be of considerable utility to chemical biologists. Herein, we report guided chemical synthesis of small molecules capable of binding to DNA bulges by virtue of their unique (spirocyclic) geometry. The agents, modeled on a natural product congener, show pronounced selectivity for specific bulged motifs and are able to enhance slipped DNA synthesis, a hallmark functional assay of bulge binding. Significantly, bulge-agent complexes demonstrate characteristic fluorescent signatures depending on bulge and flanking sequence in the oligo. It is anticipated that these signature patterns can be harnessed as molecular probes of bulged hotspots in DNA and RNA.
Jones
Graham B
GB
Bioorganic and Medicinal Chemistry Laboratories, Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA 02115, USA. grjones@neu.edu
Lin
Yiqing
Y
Xiao
Ziwei
Z
Kappen
Lizzy
L
Goldberg
Irving H
IH
D004247:DNA / Q000737:chemistry*; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D015335:Molecular Probes; D009690:Nucleic Acid Conformation; D015345:Oligonucleotide Probes; D021241:Spectrometry, Mass, Electrospray Ionization
D007202:Indicators and Reagents; D015335:Molecular Probes; D015345:Oligonucleotide Probes; D004247:DNA