New pathways for synthesis of nucleic acid analogues are being developed. A number of modifications of the diester phosphate moiety of the natural nucleic acids are being made, and the chemical and biological properties are also investigated. Derivatives containing P-F bonds which are very similar to the regular phosphates and may be biologically active, have potential therapeutic value in e.g. antisense/antigene strategies. Analogues containing P-C bonds, C-phosphonates, are also interesting in an antisense/antigene context, but in spite of this efficient pathways for their synthesis have not been developed yet. Nucleoside H-phosphonate monoesters are versatile precursors to various oligonucleotide analogues and are being studied with respect to stereochemistry and mechanistic properties.
Phospholipid-nucleoside conjugates have shown to exert tumoricidal activity and are also interesting due to their potential as drug carriers. New approaches for the synthesis of phospholipid conjugates are explored.The incorporation of boron into the nucleic acid phosphate are of medical interest since the sequence recognition properties of the nucleic acid analogue may be combined with the use of 10B in boron neutron capture therapy for the treatment of malignancies.
A family of novel carbocyclic analogs of Locked Nucleic Acids
(LNA) has been designed, developed and synthesized in the group.
The exploited so far structural scaffolds are summarized in Figure