Web Release Date: June 25,
Combinatorial Selection and Edited Combinatorial Selection of Phosphorothioate
Aptamers Targeting Human Nuclear Factor-
B RelA/p50 and RelA/RelA
and
Department of Human Biological Chemistry and Sealy Center for Structural Biology, Genetics and Department of Pathology and Center for Biodefense and Emerging Infectious Diseases and WHO Collaborating Center for Tropical Diseases, University of Texas Medical Branch, Galveston, Texas 77555, and Institute for Neurodegenerative Diseases, University of California San Francisco, San Francisco, California 94143-0518
Received December 10, 2003
Revised Manuscript Received May 6, 2004
Abstract:
Nuclear factor-B (NF-B) 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-B dimers may serve as therapeutic agents for the prevention of pathogenic
immune responses. We have selected monothiophosphate-modified aptamers, or "thioaptamers", to the
NF-B 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-B 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-B proteins within nuclear extracts
from lipopolysaccharide (LPS)-induced macrophages and B cells.
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