Hejesen, Christian6; Pedersen, Lars Kolster4; Gothelf, Kurt Vesterager7; Hansen, Nils Jakob Vest4
1 iNano-School, Science and Technology, Aarhus University2 Department of Chemistry, Science and Technology, Aarhus University3 Interdisciplinary Nanoscience Center, Science and Technology, Aarhus University4 Vipergen5 Department of Chemistry, Department of Chemistry, Science and Technology, Aarhus University6 Interdisciplinary Nanoscience Center, Science and Technology, Aarhus University7 Department of Chemistry, Department of Chemistry, Science and Technology, Aarhus University
DNA-directed synthesis of encoded combinatorial libraries of small organic compounds most often involves transfer of organic building blocks from one DNA strand to another. This requires cleavable linkers to enable cleavage of the link to the original DNA strand from which the building block is transferred. Relatively few cleavable linkers are available for DNA-directed synthesis and most often they leave an amino group at the organic molecule. Here we have extended the application of 10 aryltriazenes as traceless linkers for DNA-directed synthesis. After reaction of one building block with a building block at another DNA strand the triazene linker is cleaved and reduced with hypophosphorous acid in high yield to leave the arylgroup with a hydrogen in place of the triazene i.e. without a functional group trace. It was also demonstrated that alternatively the triazene could be converted to an azide, which was used in a cycloaddition reaction. The linker is generally stable at pH >7 and could be stored for 15 several months in a freezer without significant degradation.
Organic and Biomolecular Chemistry, 2013, Vol 11, Issue 15, p. 2493-2497