Oligonucleotides Containing Modified Sugars

Oligonucleotides containing 2 -0-aminopropyl-substituted RNA have been synthesised. The 2 -0-(aminopropyl)adenosine, 2 -0-(aminopropyl)cytidine, 2 -0-(aminopropyl)guanosine, and 2 -0-(aminopropyl)uridine (APU) were prepared 

Disaccharide nucleosides occur naturally in antibiotics and as modified nucleo- 

Seela and co-workers have synthesised DNA in which xylose entirely replaces ribose sugar.To achieve this the synthesis of the monomer reagents has been 

A Oligonucleotides Containing Modified Sugars. a-Anomeric oligoribonucleo-tldes a-rlls and a-rllu have been prepared on a solid-phase support from 

A potentially attractive route to 0-roethylnucleosldes is based on the use of the [[2-(methylthio)phenyl]thio]methyl group for the protection of primary and secondary hydroxy functions.This protecting group is stable under both acidic and basic conditions and functions as a latent 0-methyl group. For example, 5 -0-[[[2-(methylthio)phenyl]thio]methyl]-2 -deoxythymldine (105) is readily converted into 5 -0-methylthymidine in 68Z yield by treatment with tributyltin hydride and azobls(isobutyronitrile). Alternatively, deprotection to give thymidine can be accomplished using mercury (II) chloride in aqueous acetonitrile. 

A series of analogues of the decamer d(GGGAATTCCC) have been prepared in which the nucleosides are sequentially replaced by (t)-butan-l,3-diol to give oligodeoxyrlbonucleotides that lack the deoxyrlbose moiety at the chosen position. The diol unit was converted into the phosphoramidite derivative 

Dinucleotides containing a 5 -N-phosphoramldate linkage have been prepared by reaction of 5 -O-dimethoxytrityl-2 -deoxythymidine with N,N-diisopropylamino-bls(methoxy)phosphine and tetrazole.The intermediate phosphite triester was treated with a 5 -azido-2, 5 -dldeoxynucleoside and in the presence of 

4-0-i-Propyl-2 -deoxythymldine (i dT) has been incorporated into the dinucleotides d(i TpT) and d(Tpl T).In contrast to the monomers the two isopropyl methyl groups are magnetically nonequivalent and give rise to separate H and n.m.r. signals. Coupling constant data also indicate a 3 -endo sugar pucker for the i dT residue. 

5 -C-Branched thymidines bearing 5 -(S)-C-aminomethyl, 5 -(S)-C-azido-methyl, and 5 -(S)-cyanomethyl have been prepared from the key intermediate 5 - 

Beaucage and co-workers have prepared thymidine derivatives which contain an ethyl linkage inserted into the glycosidic bond and these have been transformed into reagents suitable for DNA synthesis (167a-d),  

Oligonucleotides bearing a 2 -anthracene unit have been prepared using the phosphoramidite reagent (168).The modified nucleic acid binds to both DNA and RNA but an induced change in CD due to the anthracene chromo-phore was only observed in the case of DNA and not RNA. 

A trimer oligoribonucleotide bearing a S -amino function, 2 -S -phosphodiester linkages and an acyclic sugar moiety at the 3 -nucleoside position (169) has been prepared and characterised by Pfleiderer and co-workers. 

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Oligonucleotides containing modified sugars - A method has been reported for... 

Zhang et reported the synthesis of novel L-isonucleoside (97) modified oligonueleotides containing S -CHa-extended chains at the sugar moiety and isoadenine or isothymine as the nucleobase. These were incorporated into DNA and siRNA. These modified oligonucleotides can form stable double helical structures with their complementary DNA and RNA and are stable towards nucleases when compared with the unmodified DNA. 

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