Oligonucleotides sugar modifications

Hybridon, Inc. Sugar modification 2 -0-Methyl-modified oligonucleotides W09612497 1996... 

A few hexose-based sugar modifications have been applied to oligonucleotides. 2 -Fluoro cyclohexenyl nucleic acids (CeNA) (24) have been incorporated into a DNA duplex where it was slightly destabilising but exhibited enhanced nuclease stability.A ciystal structure of RNA with (24) showed that it formed an A-type duplex not unlike that found with RNA RNA duplexes. A crystal structure of a duplex between RNA and altritol nucleic acids (25) has been reported and the hybrid structure formed an A-type helix analogous to a fully RNA duplex. Aptamers have... 

The formation of an aldehyde group on a macromolecule can produce an extremely useful derivative for subsequent modification or conjugation reactions. In their native state, proteins, peptides, nucleic acids, and oligonucleotides contain no naturally occurring aldehyde residues. There are no aldehydes on amino acid side chains, none introduced by post-translational modifications, and no formyl groups on any of the bases or sugars of DNA and RNA. To create reactive aldehydes at specific locations within these molecules opens the possibility of directing modification reactions toward discrete sites within the macromolecule. 

To avoid the problem of chirality and to improve the potency and limit the non-specific actions of AS-ODN, new compounds are required. Synthesis of new AS-ODNs has further improved their nuclease stability, enhanced of cellular uptake and affinity through modification of the base, sugar and phosphate moieties of the oligonucleotides [105-108],... 

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