Regiospecific solid-phase synthesis of branched oligoribonucleotides that mimic intronic lariat RNA intermediates

Adam Katolik, Richard Johnsson, Eric Montemayor, Jeremy G. Lackey, P. John Hart, Masad J. Damha

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

We have developed new solid phase methods for the synthesis of branched RNAs that mimic intronic lariat RNA intermediates. These methods produce branched oligoribonucleotide sequences of arbitrary length, base composition, and regiochemistry at the branchpoint junction. The methods utilize branching monomers that allow for the growth of each branch regioselectively from any of the hydroxyl positions (5′, 3′, or 2′) at the branch-point junction. The integrity and branchpoint connectivity of the synthetic products have been confirmed by HPLC and MS analysis, and cleavage of the 2′,5′ linkage by recombinant debranching enzyme. Nonhydrolyzable branched RNA analogues containing arabinose instead of ribose at the branchpoint junction were shown to inhibit debranching activity and, hence, represent "decoys" for sequestering RNA binding proteins thought to drive amyotrophic lateral sclerosis (ALS).

Original languageEnglish (US)
Pages (from-to)963-975
Number of pages13
JournalJournal of Organic Chemistry
Volume79
Issue number3
DOIs
StatePublished - Feb 7 2014

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Oligoribonucleotides
RNA
Arabinose
RNA-Binding Proteins
Ribose
Hydroxyl Radical
Monomers
Enzymes
Chemical analysis

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Regiospecific solid-phase synthesis of branched oligoribonucleotides that mimic intronic lariat RNA intermediates. / Katolik, Adam; Johnsson, Richard; Montemayor, Eric; Lackey, Jeremy G.; Hart, P. John; Damha, Masad J.

In: Journal of Organic Chemistry, Vol. 79, No. 3, 07.02.2014, p. 963-975.

Research output: Contribution to journalArticle

Katolik, Adam ; Johnsson, Richard ; Montemayor, Eric ; Lackey, Jeremy G. ; Hart, P. John ; Damha, Masad J. / Regiospecific solid-phase synthesis of branched oligoribonucleotides that mimic intronic lariat RNA intermediates. In: Journal of Organic Chemistry. 2014 ; Vol. 79, No. 3. pp. 963-975.
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