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Original Articles

Synthesis and Biochemical Activity of New Oligonucleotide Analogs

, , , , &
Pages 349-363 | Published online: 21 Jun 2008
 

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.

Acknowledgments

This work was supported by the University of Colorado. The technical assistance of Richard Shoemaker in the NMR Laboratory is gratefully acknowledged.

Notes

a Peroxyanion Solution: Solution A = 3% (w/v) aqueous LiOH (10 mL), 1.5 M 2-amino-2-methyl-1-propanol in water (15 mL), and dioxane (17.5 mL). Solution B = m-chloroperbenzoic acid (1.78 g), dioxane (32.5 mL), and aqueous 30% hydrogen peroxide (12 mL). Equal volumes are mixed just prior to synthesis.

a p = phosphate; b = borane phosphonate. b Perseptive Biosystems Voyager Biospectrometry Workstation using a previously published procedure.

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