Ultramild Protein-Mediated Click Chemistry Creates Efficient Oligonucleotide Probes for Targeting and Detecting Nucleic Acids

Lina J. Nabo, Charlotte S. Madsen, Knud Jørgen Jensen, Jacob Kongsted, Kira Astakhova

Research output: Contribution to journalJournal articleCommunication

Abstract

Functionalized synthetic oligonucleotides are finding growing applications in research, clinical studies, and therapy. However, it is not easy to prepare them in a biocompatible and highly efficient manner. We report a new strategy to synthesize oligonucleotides with promising nucleic acid targeting and detection properties. We focus in particular on the pH sensitivity of these new probes and their high target specificity. For the first time, human copper(I)-binding chaperon Cox17 was applied to effectively catalyze click labeling of oligonucleotides. This was performed under ultramild conditions with fluorophore, peptide, and carbohydrate azide derivatives. In thermal denaturation studies, the modified probes showed specific binding to complementary DNA and RNA targets. Finally, we demonstrated the pH sensitivity of the new rhodamine-based fluorescent probes in vitro and rationalize our results by electronic structure calculations.
Original languageEnglish
JournalChembiochem
Volume16
Issue number8
Pages (from-to)1163-1167
Number of pages5
ISSN1439-4227
DOIs
Publication statusPublished - 2015
Externally publishedYes

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