The solution structure of a DNA·RNA duplex containing 5-propynyl U and C; comparison with 5-Me modifications

Jeffrey I. Gyi, Daquan Gao, Graeme L. Conn, John O. Trent, Tom Brown, Andrew Lane

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


The addition of the propynyl group at the 5 position of pyrimidine nucleotides is highly stabilising. We have determined the thermodynamic stability of the DNA·RNA hybrid r(GAAGAGAAGC duplex and the effects of methyl substitutions. The incorporation of the propyne group at the 5 position gives rise to a very large stabilisation of the hybrid duplex compared with the analogous 5-Me modification. The duplexes have been characterised by gel electrophoresis and NMR spectroscopy, which indicate that methyl substitutions have a smaller influence on local and global conformation than the propynyl groups. The increased NMR spectral dispersion of the propyne-modified duplex allowed a larger number of experimental restraints to be measured. Restrained molecular dynamics in a fully solvated system showed that the propyne modification leads to substantial conformational rearrangements stabilising a more A-like structure. The propynyl groups occupy a large part of the major groove and make favourable van der Waals interactions with their nearest neighbours and the atoms of the rings. This enhanced overlap may account at least in part for the increased thermodynamic stability. Furthermore, the simulations show a spine of hydration in the major groove as well as in the minor groove involving the RNA hydroxyl groups.

Original languageEnglish
Pages (from-to)2683-2693
Number of pages11
JournalNucleic Acids Research
Issue number10
StatePublished - May 15 2003

Bibliographical note

Funding Information:
NMR spectra were recorded at the MRC Biomedical NMR Centre, Mill Hill, London UK. This work was supported by the Medical Research Council of the UK.

ASJC Scopus subject areas

  • Genetics


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