Antisense pro-drugs: 5'-ester oligodeoxynucleotides

Abstract
Oligonucleotides bearing a terminal llpophlllc group attached through a biodegradable ester bond should be useful as antisense pro-drugs with improved cellular uptake. The synthesis of 5-ester oligonucleotides is, however, problematic due to lability of the ester bond during aqueous ammonia treatment that Is commonly used for the deprotectlon of synthetic oligonucleotides. The synthesis of 5'-palmltoyl oligodeoxynucleotides was accomplished In good yield by the use of a combination of base-labile tert-butylphenoxyacetyl amino protecting groups (t-BPA), the oxalyl-CPG anchor group, and ethanolamine (EA) as a deprotectlng reagent.

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