Assessment of heat-sensitive thiophosphate protecting groups in the development of thermolytic DNA oligonucleotide prodrugs

Heat-sensitive thiophosphate protecting groups derived from the alcohol 4 or 10 have provided insights in the design of DNA oligonucleotide prodrugs. Indeed, functional groups stemming from the alcohol 9, 15, 16 or 22 may be applicable to thiophosphate protection of immunostimulatory CpG DNA motifs, whereas those originating from the alcohol 3, 5, 12, 13, 18, 20 or 22 offer adequate protection of terminal phosphodiester functions against ubiquitous exonucleases that may be found in biological environments. Functional groups derived from the alcohol 9, 15, 16, 19 or 23 are suitable for the protection of phosphodiester functions flanking the CpG motifs of immunomodulatory DNA sequences.