Improved synthesis of oligonucleotides with an allylic backbone. Oligonucleotides containing acyclic, achiral nucleoside analogues: N-1 or N-9-[3-hydroxy-2-(hydroxymethyl)prop-1-enyl]nucleobases

Organic & Biomolecular Chemistry
Britta M DahlOtto Dahl

Abstract

An improved phosphoramidite method is described to prepare oligonucleotides modified with the acyclic, achiral monomers 1. Examination of dimers, prepared on solid support or in solution, showed that phosphortriester dimers containing the allylic unit 1 were unstable towards bases, whereas phosphordiester dimers were stable. Phosphordiester dimers were obtained by replacing cyanoethyl phosphoramidites 2 with phosphoramidites 3, which gave phosphordiesters directly upon oxidation. The phosphordiester dimers were found to be stable towards capping and oxidation, but were somewhat labile towards acids. By reducing the contact time to acids during detritylation it was possible to prepare oligonucleotides containing 4 or 8 modified A, G or T units. The modified oligonucleotides hybridized to complementary DNA and RNA, although with reduced affinity (DeltaT(m) per modification -1 to -5 degrees C).

References

May 6, 1998·Bioorganic & Medicinal Chemistry·J KehlerO Dahl
Mar 23, 2001·The Journal of Organic Chemistry·A P Guzaev, M Manoharan
Apr 16, 2003·European Journal of Biochemistry·Jens Kurreck

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Citations

Apr 23, 2013·Angewandte Chemie·Phaneendrasai KarriRamanarayanan Krishnamurthy

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