Ribonucleosides are converted to deoxyribonucleosides by a biochemical process that removes the 2'-hydroxyl group, and that could have removed the 3'-hydroxyl group instead with a different enzymatic preference. This raises the question of whether there is some intrinsic chemical preference for the natural structure of DNA, with its phosphate links joining the 3' and 5' positions of adjacent bases. We have prepared DNA isomers in which we use 3'deoxynucleosides, and which have the unnatural

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... ' links. We find that they form duplexes using the normal genetic code pairings, but more weakly than does normal DNA. Computer modelling indicates some of the problems that the unnatural structure introduces.