| 摘要 |
<p>A novel approach for combining the ease of cleavage of carboxylic acid linker arms with the single phosphoramidite coupling chemistry of the universal supports useful in oligonucleotide synthesis. There is disclosed a new class of phosphoramidite reagents, linker phosphoramidites, which contain a bifunctional linker arm with a protected nucleoside linked through a 3'-ester bond on one end and a reactive phosphoramidite group or other phosphate precursor group on the other end. The phosphoramidite group on the linker phosphoramidite may be activated under the same conditions and has similar reactivity as conventional nucleoside-3'-phosphoramidite reagents lacking the intermediate linker arm. The 3'-ester linkage contained within the linker phosphoramidite has similar properties to the linkages on prederivatized supports. The ester linkage is stable to all subsequent synthesis steps, but upon treatment with a cleavage reagent, such as ammonium hydroxide, the ester linkage is hydrolyzed. This releases the oligonucleotide product with the desired 3'-hydroxyl terminus and leaves the phosphate portion of the reagent attached to the support, which is subsequently discarded.</p> |
