Synthesis and Biochemical Activity of New Oligonucleotide Analogs

Author: McCuen Heather Brummel   Noe Mary   Olesiak Magdalena   Sierzchala Agnieszka   Caruthers Marvin   Higson Adrian  

Publisher: Taylor & Francis Ltd

ISSN: 1042-6507

Source: Phosphorus, Sulfur, and Silicon and the Related Elements, Vol.183, Iss.2-3, 2008-02, pp. : 349-363

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Abstract

Borane phosphonate deoxyoligonucleotides are synthesized from 5'-O-benzhydroxybis(trimethylsilyloxy)silyl-2'-deoxynucleoside-3'-phosphoramidites. The exocyclic amines of adenine and cytosine are protected with dimethoxytrityl and trimethoxytrityl, respectively, whereas guanine protection is with N2-(9-fluorenylmethoxycarbonyl) or N2-trimethoxytrityl. Thymine is protected with N3-anisoyl. Using these synthons and under standard conditions via activation with tetrazole, condensations in excess of 99% are observed. Oxidation with either THF·BH3 or a peroxyanion solution followed by cleavage of the silyl ether with fluoride completes a cycle. Following synthesis of an appropriate oligomer, protecting groups are removed using sequentially acetic acid, a dithiolate and ammonium hydroxide. Oligodeoxynucleotide 10 mers and 12 mers having any combination of borane phosphonate and phosphate internucleotide linkages as well as all four 2'-deoxynucleotides are synthesized in isolated yields of 70-80% and characterized by phosphorus NMR and mass spectrometry.

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