Oligonucleotide boranophosphate

Studies Toward the Development of a Solid-Phase Method for the Synthesis of Oligonucleotide Boranophosphates... 

Figure 1.2 Modified nucleotides and nucleosides described in the text. (A) Nucleotides incorporated by polymerases yielding nuclease-resistant oligonucleotides. Top from left to right 2 -fluoro, 2 -amino, 2 -0-methyl. Bottom from left to right boranophosphate, phosphorothioate, 4 -thio. (B) Photosensitive residues. Left to right 5-bromo-U, 2-(2-nitrophenyl)ethyl T, 2-(2-nitrophenyl)propyl T. (C) Amino-imino equilibrium used in 2D-SELEX (see the text).

A previously-reported bicyclic 3 -aminonucleoside has now been converted to the dinucleotide building block 225, which caused a reduction in values when incorporated into oligonucleotides. There has been an extended and expanded account of the preparation of dideoxynucleoside boranophosphates through the intermediacy of H-phosphonate diesters. The conversion of these to the boranophosphates proceeds with retention of configuration. ... 

Boranophosphate linkages have been of interest because they mimic natural DNA, and may have potential in diagnostic and therapeutic applications (boron neutron capture therapy). Boranophosphate-modified siRNA has been shown to possess potent gene-silencing properties compared to the unmodified siRNA. Two novel methods have been reported for the synthesis of boranophosphate oligonucleotides, one using phosphoramidite chemistry, the other boranophosphotriester chemistry. Dinucleoside boranophosphates and a-borano nucleoside triphosphates have also been described. " ... 

Reaction of dimer 1 with 5 -DMT-thymidine phosphoramidite, followed by Me2S BH3, results in the formation of trimer 3 (trinucleoside boranophosphate methylester, 3) (see Scheme I) in which both intemu-cleotide linkages are boranophosphate methyl ester groups. This reaction was carried out with equal molar amounts of 1 and DMT-thymidine-phosphoramidite, and the yield of 3 was only 22.4% prior to and 5.2% after HPLC. Yet a large proportion (ca. 66%) of dimer 1 was recovered unreacted. Clearly, the procedure must be optimized to obtain a 99%+ coupling yield before it could be used for practical synthesis of oligonucleotides. In a second experiment performed in an NMR tube, 5 Eq of amidite resulted in >95% conversion. 

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