SYNTHESIS OF OLIGONUCLEOTIDE ANALOGS WITH MODIFIED BACKBONES

The research activity in the general area of modified oligonucleotides and their dephospho analogues is summarized. The general criteria for the design of oligomers with altered backbones, namely charge, hydration and conformational freedom of the internucleosidyl linkage, are described. The flexible and semi-rigid polyamide linkages are emphasized which are best suited to adapt to the solid phase synthetic methodologies, at the same time satisfying the necessary physical requirements for optimum binding to form a duplex or triplex. A novel approach is described which takes advantage of the established peptide chemistry in the synthesis of oligonucleosides with an amino acid backbone. A discussion of the future direction for the synthesis and application of these polymers is included.