Programmable oligomers targeting 5'-GGGG-3' in the minor groove of DNA and NF-kappaB binding inhibition.
A series of hairpin oligomers containing benzimidazole (Bi) and imidazopyridine (Ip) rings were synthesized and screened to target 5'-WGGGGW-3', a core sequence in the DNA-binding site of NF-kappaB, a prolific transcription factor important in biology and disease. Five Bi and Ip containing oligomers bound to the 5'-WGGGGW-3' site with high affinity. One of the oligomers (Im-Im-Im-Im-gamma-Py-Bi-Py-Bi-beta-Dp) was able to inhibit DNA binding by the transcription factor NF-kappaB.
Chenoweth
David M
DM
The Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Poposki
Julie A
JA
Marques
Michael A
MA
Dervan
Peter B
PB
D001483:Base Sequence; D001665:Binding Sites / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D006571:Heterocyclic Compounds / Q000138:chemical synthesis / Q000494:pharmacology; D006860:Hydrogen Bonding; D007120:Immunochemistry; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000187:drug effects* / Q000378:metabolism*; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides / Q000037:antagonists & inhibitors*
D006571:Heterocyclic Compounds; D016328:NF-kappa B; D009841:Oligonucleotides; D004247:DNA