Factors influencing hairpin oligonucleotide cyclization by the uncatalyzed alkyne-azide cycloaddition (AAC) reaction

El-Sagheer, Afaf H.; Brown, Tom

doi:10.1351/PAC-CON-09-10-42

Pure Appl. Chem., 2010, Vol. 82, No. 8, pp. 1599-1607

http://dx.doi.org/10.1351/PAC-CON-09-10-42

Published online 2010-05-13

Factors influencing hairpin oligonucleotide cyclization by the uncatalyzed alkyne-azide cycloaddition (AAC) reaction

Afaf H. El-Sagheer^1,2 and Tom Brown²*

¹ Chemistry Branch, Department of Science and Mathematics, Faculty of Petroleum and Mining Engineering, Suez Canal University, Suez, Egypt
² School of Chemistry, University of Southampton, Highfield, Southampton, SO17 1BJ, UK

Abstract: Cyclization of short hairpin oligonucleotides (ODNs) containing unactivated alkynes and alkyl azides produces triazole-linked products slowly in the absence of Cu^I catalysis. The factors affecting the rate of this cycloaddition reaction have been investigated on a variety of hairpin sequences. The reaction proceeds best at intermediate concentrations of sodium chloride, but is inhibited by phosphate and Tris buffers. It is accelerated by increasing the temperature provided that Watson–Crick base pairing can occur. The rationale for these observations is discussed.