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

Biochemistry
Suzanne E BassettDavid G Gorenstein

Abstract

Nuclear factor-kappaB (NF-kappaB) 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-kappaB dimers may serve as therapeutic agents for the prevention of pathogenic immune responses. We have selected monothiophosphate-modified aptamers, or "thioaptamers", to the NF-kappaB 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-kappaB 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-kappaB proteins within nuclear extracts from lipopolysaccharide (LPS)-induced macrophages and B cells.

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Citations

Mar 24, 2009·Chemical Reviews·Juewen LiuYi Lu
Aug 6, 2009·Oligonucleotides·Kristina W Thiel, Paloma H Giangrande
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Dec 6, 2006·Annals of the New York Academy of Sciences·Xianbin YangDavid G Gorenstein
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Sep 1, 2015·Biomedicines·Joy Sebastian Prakash, Karunanithi Rajamanickam
Oct 16, 2010·Analytical Chemistry·Ariel H HechtAnson V Hatch

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