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. ; © 2006 Elsevier. Received 13 September 2006, Revised 23 October 2006, Accepted 23 October 2006, Available online 26 October 2006. We thank Eric J. Fechter for the preparation of plasmid pEF16 and Thomas Leung for valuable discussions. We thank The National Institutes of Health for grant support and a NRSA predoctoral training grant to J.A.P. We also thank the Parsons Foundation for a fellowship to M.A.M. ; Accepted Version - nihms15550.pdf