2'-Alkynylnucleotides: A Sequence- and Spin Label-Flexible Strategy for EPR Spectroscopy in DNA

M. M. Haugland, A. H. El-Sagheer, R. J. Porter, J. Pena, T. Brown, E. A. Anderson and J. E. Lovett. J. Am. Chem. Soc. 2016.


Electron paramagnetic resonance (EPR) spectroscopy is a powerful method to elucidate molecular structure through the measurement of distances between conformationally well-defined spin labels. Here we report a sequence-flexible approach to the synthesis of double spin-labeled DNA duplexes, where 2?-alkynylnucleosides are incorporated at terminal and internal positions on complementary strands. Post-DNA synthesis copper-catalyzed azide–alkyne cycloaddition (CuAAC) reactions with a variety of spin labels enable the use of double electron–electron resonance experiments to measure a number of distances on the duplex, affording a high level of detailed structural information.