Synthesis of a Nonhydrolyzable Nucleotide Phosphoroimidazolide Analogue That Catalyzes Nonenzymatic RNA Primer Extension.

ABSTRACT: We report the synthesis of guanosine 5'-(4-methylimidazolyl)phosphonate (ICG), the third member of a series of nonhydrolyzable nucleoside 5'-phosphoro-2-methylimidazolide (2-MeImpN) analogues designed for mechanistic studies of nonenzymatic RNA primer extension. The addition of a 2-MeImpN monomer to a primer is catalyzed by the presence of a downstream activated monomer, yet the three nonhydrolyzable analogues do not show catalytic effects under standard mildly basic primer extension conditions. Surprisingly, ICG, which has a pK_a similar to that of 2-MeImpG, is a modest catalyst of nonenzymatic primer extension at acidic pH. Here we show that ICG reacts with 2-MeImpC to form a stable 5'-5'-imidazole-bridged guanosine-cytosine dinucleotide, with both a labile nitrogen-phosphorus

SUBMITTER: Tam CP 

PROVIDER: S-EPMC6326531 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature