Phototriggered DNA phosphoramidate ligation in a tandem 5´-amine deprotection / 3´-imidazole activated phosphate coupling reaction

Jonathan Cape, Joseph B. Edson, Liam P. Spencer, Michael S. DeClue, Hans-Joachim Ziock, Sarah Maurer, Steen Rasmussen, Pierre-Alain Monnard, James M. Boncella

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

We report the preparation and use of an N-methyl picolinium carbamate protecting group for applications in a phototriggered nonenzymatic DNA phosphoramidate ligation reaction. Selective 5′-amino protection of a modified 13-mer oligonucleotide is achieved in aqueous solution by reaction with an N-methyl-4-picolinium carbonyl imidazole triflate protecting group precursor. Deprotection is carried out by photoinduced electron transfer from Ru(bpy)32+ using visible light photolysis and ascorbic acid as a sacrificial electron donor. Phototriggered 5′- amino oligonucleotide deprotection is used to initiate a nonenzymatic ligation of the 13-mer to an imidazole activated 3′-phospho-hairpin template to generate a ligated product with a phosphoramidate linkage. We demonstrate that this methodology offers a simple way to exert control over reaction initiation and rates in nonenzymatic DNA ligation for potential applications in the study of model protocellular systems and prebiotic nucleic acid synthesis.
Original languageEnglish
JournalBioconjugate Chemistry
Volume23
Issue number10
Pages (from-to)2014-2019
ISSN1043-1802
DOIs
Publication statusPublished - 2012

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