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.
Molecular probes of DNA bulges: functional assay and spectroscopic analysis. Publishing Authors By Initials
Chemical & Substance for Abstract: Molecular probes of DNA bulges: functional assay and spectroscopic analysis. Information
Substance Name: DNA
Registry Number: 9007-49-2
Grant and Affiliation Information for Molecular probes of DNA bulges: functional assay and spectroscopic analysis.
AFFILIATION: Bioorganic and Medicinal Chemistry Laboratories, Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA 02115, USA. grjones@neu.edu
Country: England
AGENCY: United States NIGMS
GRANT: R01GM57123
ACRONYM: GM
MEDLINETA: Bioorg Med Chem
REFSOURCE:
DATABASENAME:
ACCESSION NUMBER:
Number Hits: 0
Molecular probes of DNA bulges: functional assay and spectroscopic analysis Related Publications