Synthesis and characterization of a carbamate-linked oligonucleoside

✍ Scribed by James M Coull; Dean V Carlson; H.Lee Weith

• Book ID: 104233381
• Publisher: Elsevier Science
• Year: 1987
• Tongue: French
• Weight: 317 KB
• Volume: 28
• Category: Article
• ISSN: 0040-4039
• DOI: 10.1016/s0040-4039(01)80978-3

✦ Synopsis

Reaction of 5'-0-dimethoxytritylthymidine with l,l'-carbonyldiimidazole gave the 3'-0-carbonylimidazolide, which was condensed in high yield with 5'-amino-5'-deoxythymidine to produce a dinucleoside containing a 3'-0-5'-N-carbamoyl linkage.

Four repetitions of carbonyl imidazolide formation and condensation produced a carbamate-linked hexamer.

Hydrolytic and thermal denaturation studies did not indicate the presence of intramolecular base stacking. Oligonucleotide analogues containing non-ionic internucleoside linkages are of interest due to their potential as anti-viral agents, as repressors of gene expression at the transcriptional and translational levels, and as models for the study of nucleic acid structure and function. Some of the analogues reported to date contain methylphosphonate cl), carbonate (2), oxyacetamide (3) and carbamate (3,4) internucleoside linkages. The oxyacetamide and carbamate analogues are attractive due to their stability over a wide pH range and their resistance to enzymatic degradation. Furthermore, in contrast to the methylphosphonate analogues, they possess linkages which are achiral, thus avoiding the difficult separation of diastereomers during their synthesis and purification.