Syntheses and Properties of Oligothymidylate Analogs Containing Stereoregulated Phosphoromorpholidate and Phosphodiester Linkages in an Alternating Manner
- 1 July 1990
- journal article
- research article
- Published by Oxford University Press (OUP) in Bulletin of the Chemical Society of Japan
- Vol. 63 (7) , 1929-1936
- https://doi.org/10.1246/bcsj.63.1929
Abstract
Syntheses and some properties of undecathymidylate analogs containing stereoregulated phosphoromorpholidate and phosphodiester linkages in an alternating manner are described. These analogs were easily obtained by the phosphorobisamidite approach starting from pre-separated diastereomerically pure dithymidine phosphoromorpholidate derivatives. Both isomers were found to be high resistant to nucleases, in comparison with natural oligothymidylate; the phosphodiester linkages except 3’-end in the isomers were not cleaved by SI nuclease and both isomers were very slowly degraded by phosphodiesterase I and micrococcal nuclease. The rate of each degradation was dependent on the configuration of phosphoromorpholidate linkage in each isomer. The UV and CD spectral studies show that one of the isomer can interact with poly(dA) to give B-type duplex possessing the same thermal stability as natural oligothymidylate-poly(dA) duplex and the other isomer does not interact with poly(dA) under the comparable conditions.Keywords
This publication has 16 references indexed in Scilit:
- Synthesis of Bis(deoxyribonucleoside) Phosphoromorpholidate Derivatives for Oligodeoxyribonucleotide Preparation by Use of a Selective Phosphitylating ReagentBulletin of the Chemical Society of Japan, 1989
- A simple preparation of 5′-o-dimethoxytrityl deoxyribonucleoside 3′-o-phosphorbisdiethylamidites as useful intermediates in the synthesis of oligodeoxyribonucleotides and their phosphorodiethylamidate analogs on a solid supportTetrahedron, 1989
- Synthesis, isolation and characterization of diastereochemically pure dithymidine phosphormorpholidate derivativesTetrahedron Letters, 1989
- Techniques for using antisense oligodeoxyribonucleotides to study gene expressionAnalytical Biochemistry, 1988
- Phosphorothioate analogs of oligodeoxynucleotides: inhibitors of replication and cytopathic effects of human immunodeficiency virus.Proceedings of the National Academy of Sciences, 1987
- Deoxynucleoside H-Phosphonate diester intermediates in the synthesis of internucleotide phosphate analoguesTetrahedron Letters, 1986
- Reversed-phase high-performance liquid chromatographic separation of diastereomeric phosphorothioate analogues of oligodeoxyribonucleotides and other backbone-modified congeners of dnaJournal of Chromatography A, 1985
- Preparation of oligodeoxyribonucleoside methylphosphonates on a polystyrene supportNucleic Acids Research, 1983
- Oligodeoxythymidylate: polydeoxyadenylate and oligodeoxyadenylate: polydeoxythymidylate interactionsBiochemistry, 1969
- An Improved Synthesis of 5-Substituted TetrazolesJournal of the American Chemical Society, 1958