Antisense pro-drugs: 5'-ester oligodeoxynucleotides.
Oligonucleotides bearing a terminal lipophilic 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 deprotection of synthetic oligonucleotides. The synthesis of 5'-palmitoyl 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 deprotecting reagent.
Polushin
N N
NN
Cancer Pharmacology Section, Georgetown University Medical Center, Washington DC 20007.
Cohen
J S
JS
D000215:Acylation; D001483:Base Sequence; D004952:Esters / Q000138:chemical synthesis*; D019856:Ethanolamine; D004983:Ethanolamines; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000138:chemical synthesis*; D016376:Oligonucleotides, Antisense / Q000138:chemical synthesis*; D010168:Palmitates / Q000138:chemical synthesis; D011355:Prodrugs / Q000138:chemical synthesis*
D004952:Esters; D004983:Ethanolamines; D009838:Oligodeoxyribonucleotides; D016376:Oligonucleotides, Antisense; D010168:Palmitates; D011355:Prodrugs; D019856:Ethanolamine