On the Stereochemistry of C3'-O-P-CH2-O-C4'' Phosphonate Internucleotide Bond, a Phosphate Isostere

The work deals with structural evaluation of the internucleotide phosphonate C3'-O-P-CH2-O-C4'' linkage which is an isosteric alternative to natural phosphodiester bond. A thorough description of its stereochemical features was made possible now by matching the results from additional NMR data obtained from the synthesised (13)C-labeled dimeric model compounds and the new findings provided by the extended MDS and ab initio studies. It completed the earlier assumptions. The obtained overall picture in terms of specifying the linkage conformational preferences shows explicitly why the respective phosphonate oligonucleotides differ in properties from those with related phospodiester chain.