DNA/RNA Oligos — Click Chemistry

Click chemistry is a modern synthetic approach for the modular assembly of more complex molecules from “simpler” building blocks [1,2]. In the click reaction an azide funtionalized component is coupled to an alkynyl functionalized building block to form a “bifunctional” conjugate. Since click chemistry is compatible with biomolecules in aqueous environment, this type of reaction is particularly useful to attach molecular probes to DNA [3,4]. The key advantage of the click reaction is its bioorthogonality1, since both reaction partners the azide and the alkyne group are not present in natural systems.






In the context of custom-made synthetic DNA oligonucleotides the click approach is often used to conjugate an azide functionalized molecular probe to an oligonucleotide containing an alkynyl residue (or vice versa).




Due to the unique characteristics of the click reaction, DNA and RNA oligonucleotides specifically labelled at multiple sites are now synthetically accessible. Hence click chemistry has opened a door to a new world of modified oligonucleotides which were so far virtually impossible to synthesize.




The most frequently applied type of click reaction uses Cu(I) as catalyst (copper assisted cycloaddition; CuAAC). A copper-free alternative has been developed for cases where the presence of copper is (potentially) harmful to your system. To avoid copper in the DNA probes, the more reactive alkyne residue dibenzocyclooctyne (DBCO) is applied to the click reaction [5-8].


The importance of the click reaction in the field of oligonucleotides is still growing. If you want to learn more about this exciting technology, please see the section “Useful Links and References” further below.  

We would like to invite you to send us your request (info@microsynth.ch) by indicating your sequence & modifications demands as well as your foreseen application. Microsynth would then check your inquiry and come back to you with a customized quote suggesting you a reasonable and cost-effective synthesis approach for the desired biomolecule. 

How to Order?
  • Enter our webshop
  • Click on DNA and metRNA in the "Oligonucleotide" domain
  • Select Normal Entry in order to type or copy/paste the desired sequence information
  • Follow the further instructions
  • Important: For more complex molecules (e.g. several internal modifications, specific modifiers etc.) please first contact us at Microsynth and request your customized offer! 

Useful Links and References

Click chemistry related information:


Click chemistry related information:

Copper-free click chemistry related information:




  1. El-Sagheer AH, Brown T. Chem Soc Rev. Chem. Soc. Rev., 2010,39, 1388-1405
  2. V.V. Rostovtsev, Green, L.G., Fokin, V.V. and Sharpless, K.B., Angew Chem Int Ed, 2002, 41, 2596-2599.
  3. R. Huisgen, Angew Chem Int Ed, 1963, 2, 565-598. 
  4. Y.H. Zhang, et al., Tetrahedron, 2007, 63, 6813-6821. 
  5. I.S. Marks, et al., Bioconjugate Chemistry, 2011, 22, 1259-1263. 
  6. Becer CR, Hoogenboom R, and Schubert US, Angew. Chem. Int. Ed. 2009, 48, 2–11 
  7. J. Gierlich, G. A. Burley, P. M. E. Gramlich, D. M. Hammond, T. Carell, Org. Lett. 2006, 8, 3639-3642. F. Seela, V.  R. Sirivolu, Chem. Biodiversity 2006, 3, 509-514.
  8. P. M. E. Gramlich, S. Warncke, J. Gierlich, T. Carell, Angew. Chem. 2008, 120, 3491 - 3493; Angew. Chem. Int.  Ed. 2008, 47, 3442– 3444.



1 Bioorthogonal is defined as: no interference of functional groups existing in biomolecules with the desired reaction. Hence no side products are formed with DNA, peptides, or other biomolecules.



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