Click Chemistry in DNA/RNA Synthesis

Due to its unique bioorthogonality the Click reaction is very useful also in any oligonucleotide synthesis. Simple or no workup and purification of the product are further advantages. However, the use of this method for DNA modification has been somewhat delayed by the fact that copper ions damage DNA, typically yielding strand breaks [1]. As these problems have now been overcome by the use of copper(I)-stabilizing ligands (e.g. tris(benzyltriazolylmethyl)amine, TBTA [2], Carell et al. and Seela et al. discovered that the CuAAC reaction can be used to functionalize alkyne-modified DNA nucleobases with extremely high efficiency [3,4].

A broad field of applications opens by using DNA Click components:

• DNA and RNA labelling: incorporation of alkyne-phosphoramidites in oligos followed by labelling with azido markers [7]
• PCR assays, PCR primers and labelling of large fragments with alkyne triphosphates in nucleotide mixtures; labelling PCR-fragments with azido markers [8]
• Dendron building blocks for Click chemistry
• Dendron building blocks for Click chemistry

Microarrays with phosphoramidites, triphosphates or oligonucleotides to set up microarrays; Nanoparticles, Bioconjugation.