An attractive strategy for nucleic acid conjugation involves the Cu(I)-catalyzed click reaction between terminal alkynes and azides. While 5-Ethynyl-dU in oligonucleotides has been reported to undergo the click reaction,⁽¹⁾ the short rigid nature of the alkyne group severely limits its application for this purpose. 5-Octadiynyl-dU CE-Phosphoramidite (BA0308)⁽²⁾ is a much superior reagent for the installation of an alkyne-bearing nucleoside into an oligonucleotide when click reactions are contemplated. The terminal alkyne is more flexible and extends farther away from the pyrimidine ring, thereby allowing more efficient ligation via click chemistry, even when multiple ligations to a single oligo are desired. Interestingly, the 5-Octadiynyl-dU modification gives a slight stabilization of DNA duplexes, much like the well-known effect of propynyl-dU modification.^2(a)

5-Propargyloxy-dU CE-Phosphoramidite (BA0174) is an analogous reagent to BA0308 for the facilitation of oligo click ligations. The intermediate length of the alkyne appendage allows for efficient ligation. We also offer the related nucleoside 5-(Propargyloxy)-2'-deoxyuridine (PY7712).

These compounds are sold under license from Baseclick GmbH, and the purchase of these products for use in applications relating to copper catalyzed azide-alkyne cycloaddition chemistry (“Click Chemistry”) includes a limited, nontransferable license to intellectual property owned by TSRI to use this product solely for internal non-commercial research activities and specifically excludes clinical, therapeutic, or diagnostic use in humans or animals. Information regarding a license for commercial use in Click Chemistry may be obtained directly from The Scripps Research Institute, 10550 N. Torrey Pines Rd., La Jolla, CA 92037, or by contacting 858-784-8140 or click@scripps.edu.

Ref:

1. Gierlich, J.; Burley, G. A.; Gramlich, P. M. E.; Hammond, D. M.; Carell, T. Org. Lett. 2006, 8, 3639-3642.
2. (a) Seela, F.; Sirivolu, V. R. Helv. Chim. Acta 2007, 90, 535-552. (b) Seela, F.; Sirivolu, V. R. Chem. Biodiversity 2006, 3, 509-514. Gierlich, J.; Burley, G. A.; Gramlich, P. M. E.; Hammond, D. M.; Carell, T. Org. Lett. 2006, 8, 3639-3642. (c) Hammond, D. M.; Manetto, A.; Gierlich, J.; Azov, V. A.; Gramlich, P. M. E.; Burley, G. A.; Maul, M.; Carell, T. Angew. Chem. Int. Ed. 2007, 46, 4184-4187. (d) Rozkiewicz, D. I.; Gierlich, J.; Burley, G. A.; Gutsmiedl, K.; Carell, T.; Ravoo, B. J.; Reinhoudt, D. N. ChemBioChem 2007, 8, 1997-2002.