Small-molecule-dependent split aptamer ligation

Ashwani K. Sharma, Jennifer M. Heemstra

Research output: Contribution to journalArticlepeer-review

79 Scopus citations


Here we describe the first use of small-molecule binding to direct a chemical reaction between two nucleic acid strands. The reported reaction is a ligation between two fragments of a DNA split aptamer using strain-promoted azide-alkyne cycloaddition. Utilizing the split aptamer for cocaine, we demonstrate small-molecule-dependent ligation that is dose-dependent over a wide range of cocaine concentrations and is compatible with complex biological fluids such as human blood serum. Moreover, studies of split aptamer ligation at varying salt concentrations and using structurally similar analogues of cocaine have revealed new insight into the assembly and small-molecule binding properties of the cocaine split aptamer. The ability to translate the presence of a small-molecule target into the output of DNA ligation is anticipated to enable the development of new, broadly applicable small-molecule detection assays.

Original languageEnglish
Pages (from-to)12426-12429
Number of pages4
JournalJournal of the American Chemical Society
Issue number32
StatePublished - Aug 17 2011


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