Combinatorial selection and edited combinatorial selection of phosphorothioate aptamers targeting human nuclear factor-κB RelA/p50 and RelA/RelA

Suzanne E. Bassett, Susan M. Fennewald, David J. King, Xin Li, Norbert K. Herzog, Robert Shope, Judy F. Aronson, Bruce A. Luxon, David G. Gorenstein

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Nuclear factor-κB (NF-κB) transcription factors are important in regulating the immune response and play critical roles in the pathogenesis of chronic inflammatory diseases and a variety of human cancers. Agents that target specific NF-κB dimers may serve as therapeutic agents for the prevention of pathogenic immune responses. We have selected monothiophosphate- modified aptamers, or "thioaptamers", to the NF-κB p50/RelA heterodimer using combinatorial selection techniques. We also utilized a "double sieve" or editing approach for the generation of thioaptamers with enhanced selectivity to the RelA/RelA homodimer. The thioaptamers from these selections and our previous selections on the p50/p50 and RelA/RelA homodimers all had unique sequences and bound tightly to the recombinant NF-κB dimers against which they were selected. The selected thioaptamers also appear to maintain their selectivity and specificity among other cellular proteins, because they have the ability to bind NF-κB proteins within nuclear extracts from lipopolysaccharide (LPS)-induced macrophages and B cells.

Original languageEnglish (US)
Pages (from-to)9105-9115
Number of pages11
JournalBiochemistry
Volume43
Issue number28
DOIs
StatePublished - Jul 20 2004

ASJC Scopus subject areas

  • Biochemistry

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    Bassett, S. E., Fennewald, S. M., King, D. J., Li, X., Herzog, N. K., Shope, R., Aronson, J. F., Luxon, B. A., & Gorenstein, D. G. (2004). Combinatorial selection and edited combinatorial selection of phosphorothioate aptamers targeting human nuclear factor-κB RelA/p50 and RelA/RelA. Biochemistry, 43(28), 9105-9115. https://doi.org/10.1021/bi036220h