An Extended Phosphate Linkage: Synthesis, Hybridization and Modeling Studies of Modified Oligonucleotides
- 1 July 1996
- journal article
- research article
- Published by Taylor & Francis in Nucleosides and Nucleotides
- Vol. 15 (7-8) , 1383-1395
- https://doi.org/10.1080/07328319608002438
Abstract
Novel stretched oligonucleotides (A-D) containing a 3′-α-C-methylene phosphodiester bridge (5-atoms long) have been synthesized on an automated synthesizer utilizing phosphoramidite chemistry. The key building-block 1-[3′-O-β-cyanoethyldiisopropylaminophosphiryl-2,3-dideoxy-5-O-dimethoxytriphenylmethyl-3-C-(hydroxymethyl)-β-D-erythro-pentofuranosyl]thymine (21) was prepared in a stereoselective manner from thymidine. Hybridization studies indicated a drop (1.8–3.0°C/mod.) in affinity for the complementary RNA and DNA targets. Molecular modeling results indicated that the 5-atom modified backbone had a different geometry around the phosphodiester linkage compared to the natural phosphodiester linkage. The stretched backbone may not be useful for antisense or triplex constructs, however it may find applications in biochemical/enzyme studies.Keywords
This publication has 31 references indexed in Scilit:
- Synthesis of a Carboxamide Linked UBr∗UBrDimer–Duplex and Triplex Stabilities of the Corresponding OligodeoxynucleotidesNucleosides and Nucleotides, 1995
- Antisense OligonucleotidesAccounts of Chemical Research, 1995
- Synthesis and Characterization of Short Oligonucleotide Segments Containing Nonnatural Internucleoside Amine- and Amide LinkagesNucleosides, Nucleotides and Nucleic Acids, 1995
- Synthesis of an oxyamide linked nucleotide dimer and incorporation into antisense oligonucleotide sequencesJournal of the Chemical Society, Chemical Communications, 1994
- Synthesis of a carboxamide linked T*T dimer and its incorporation in oligonucleotidesNucleic Acids Research, 1993
- Oligonucleotide Analogs Containing Dephospho- Internucleoside LinkagesPublished by Springer Nature ,1992
- Synthesis of [3t̄'(O)→-5t̄'(c)]-oxyacetamido linked nucleosidesTetrahedron, 1990
- Synthetic analogues of polynucleotides. Part VIII. Analogues of oligonucleotides containing carboxymethylthymidineJournal of the Chemical Society, Perkin Transactions 1, 1972
- The preparation of dinucleoside carbonatesJournal of the Chemical Society D: Chemical Communications, 1969
- Synthetic Analogues of PolynucleotidesNature, 1968