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RNA Cloaking by Reversible Acylation
Author(s) -
Kadina Anastasia,
Kietrys Anna M.,
Kool Eric T.
Publication year - 2018
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201708696
Subject(s) - rna , acylation , azide , chemistry , nucleic acid , folding (dsp implementation) , aptamer , biochemistry , combinatorial chemistry , stereochemistry , biophysics , organic chemistry , microbiology and biotechnology , biology , electrical engineering , gene , engineering , catalysis
We describe a selective and mild chemical approach for controlling RNA hybridization, folding, and enzyme interactions. Reaction of RNAs in aqueous buffer with an azide‐substituted acylating agent (100–200 m m ) yields several 2′‐OH acylations per RNA strand in as little as 10 min. This poly‐acylated (“cloaked”) RNA is strongly blocked from hybridization with complementary nucleic acids, from cleavage by RNA‐processing enzymes, and from folding into active aptamer structures. Importantly, treatment with a water‐soluble phosphine triggers a Staudinger reduction of the azide groups, resulting in spontaneous loss of acyl groups (“uncloaking”). This fully restores RNA folding and biochemical activity.