Oligodeoxynucleotides containing 2'-C-branched nucleosides with an amide or nitrile appended to either a one or two carbon alkyl chain have been synthesised. The phosphoramidites of the 2'-C-modified nucleosides were prepared and incorporated into the oligonucleotides using automated DNA synthesis. The duplex stability with complementary RNA and DNA was measured by UV melting experiments, in order to assess whether the amide/nitrile function could induce any duplex stability without the presence of the 2'-oxygen. The duplex stabilities of the oligonucleotides containing the 2'-C-modifications were decreased in the absence of the 2'-oxygen. (c) 2006 Published by Elsevier Ltd.