An extended phosphate linkage: Synthesis, hybridization and modeling studies of modified oligonucleotides

Novel stretched oligonucleotides (A-D) containing a 3'-alpha-C-methylene phosphodiester bridge (5-atoms long) have been synthesized on an automated synthesizer utilizing phosphoramidite chemistry. The key building-block 1-[3 ''-O-beta-cyanoethyldiisopropylaminophosphiryl-2,3 -dideoxy-...

Full description

Saved in:
Bibliographic Details
Published inNucleosides & nucleotides Vol. 15; no. 7-8; pp. 1383 - 1395
Main Authors Haly, B, Bellon, L, Mohan, Sanghvi, Y
Format Journal Article
LanguageEnglish
Published NEW YORK Marcel Dekker Inc 01.07.1996
Subjects
Biochemistry & Molecular Biology
Life Sciences & Biomedicine
Science & Technology
THYMIDINE
OLIGODEOXYNUCLEOTIDE ANALOGS
DYNAMICS
DIMER
BACKBONES
STABILITY
Online AccessGet more information

Cover

More Information
Summary:Novel stretched oligonucleotides (A-D) containing a 3'-alpha-C-methylene phosphodiester bridge (5-atoms long) have been synthesized on an automated synthesizer utilizing phosphoramidite chemistry. The key building-block 1-[3 ''-O-beta-cyanoethyldiisopropylaminophosphiryl-2,3 -dideoxy-5-O-dimethoxytriphenylmethyl-3-C-(hydroxymethyl)-beta-D-erythro-pentofuranosyl]thymine (21) was prepared in a stereoselective manner from thymidine. Hybridization studies indicated a drop (1.8-3.0 degrees 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 tripler constructs, however it may find applications in biochemical/enzyme studies.
ISSN:0732-8311
DOI:10.1080/07328319608002438