| Abstract
| - Several thermolytic CpG-containing DNA oligonucleotides analogous to 1 have been synthesized to serveas potential immunotherapeutic oligonucleotide prodrug formulations for the treatment of infectious diseasesin animal models. Specifically, the CpG motif (GACGTT) of each DNA oligonucleotide has beenfunctionalized with either the thermolabile 4-hydroxy-1-butyl or the 4-phosphato-/thiophosphato-1-butylthiophosphate protecting group. This functionalization was achieved through incorporation of activateddeoxyribonucleoside phosphoramidite 8b into the oligonucleotide chain during solid-phase synthesis and,optionally, through subsequent phosphorylation effected by phosphoramidite 9. Complete conversion ofCpG ODNs hbu1555, psb1555, and pob1555 to CpG ODN 1555 (homologous to 2) occurred underelevated temperature conditions, thereby validating the function of these diastereomeric oligonucleotidesas prodrugs in vitro. Noteworthy is the significant increase in solubility of CpG ODN psb1555 and CpGpob1555 in water when compared to that of neutral CpG ODN fma1555 (homologous to 1).
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