A traceless aryl-triazene linker for DNA-directed chemistry

Hejesen C1, Petersen LK, Hansen NJ, Gothelf KV.

Org Biomol Chem. 2013 Apr 21;11(15):2493-7. doi: 10.1039/c3ob27504c. Epub 2013 Feb 26.


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 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 aryl group 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 several months in a freezer without significant degradation.

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