Novel oligonucleotide analogues based on morpholino nucleoside subunits – Antisense technologies: New chemical possibilities

Even several decades after pioneer publications there is continued interest in the construction and synthesis of a variety of novel oligonucleotide analogues. The first oligonucleotide analogues which had a regular, predetermined structure containing nucleoside units joined with carbonate, carbamate, hydroxyacetate and hydroxyacetamide tethers have been developed in the 1970s. Further progress in oligonucleotide synthetic methods during the 1980s stimulated the development of a variety of oligonucleotide analogues containing modified carbohydrate and phosphate backbones. Particular attention has been given to the PNA (peptide nucleic acids), morpholino, and negatively charged PNA oligonucleotide analogues, which showed the most promise in a number of biological applications, such as diagnostics, nucleic acid analyses, and gene expression. The cost of parent compounds and oligonucleotide analogue synthesis is one of the most limiting factors to broad application. Studies that succeed in resolving this cost problem in the most effective way would be beneficial. Herein is presented a short review on oligonucleotide analogues that can be synthesized from inexpensive parent compounds — ribonucleosides — with or without the protection of heterocyclic bases, and with minimal protection of other reactive functions.