MOLECULAR MODELING OF ACYCLIC POLYAMIDE OLIGONUCLEOTIDE ANALOGS

The feasibility of replacing the sugar-phosphate backbone of the nucleic acids with a polyamide-type backbone has been investigated by using molecular modeling techniques that examine the ability of the acyclic backbone to adopt low energy conformations that conform to the nucleic acid A- and B-form helices. Of the several backbone possibilities examined (nylons, polyurethanes, polypeptides), the most favorable appear to be those derived from a polypeptide. For most of the cases studied, the models predict a preference for binding of a given backbone type to either A- or B-form targets and, in some cases, suggest an orientational bias for direction along the helical axis, or a preferred stereochemistry at stereogenic atoms in the backbone.