THE APPLICATION OF THE AMB PROTECTIVE GROUP IN THE SOLID-PHASE SYNTHESIS OF METHYLPHOSPHONATE DNA ANALOGS

Partially methylphosphonate-modified oligodeoxynucleotides were synthe sized on solid-phase by employing the easily removable 2-(acetoxymethy l)benzoyl (AMB) group as base-protecting group. Although a rapid AMB d eprotection can be accomplished in methanolic potassium carbonate, the lability of the methylphosphonate linkage towards potassium carbonate /methanol excludes the use of this deprotection reagent. Thus, saturat ed ammonia solution in methanol was investigated as an alternative rea gent for AMB removal. It is demonstrated that the combination of the A MB protective group and ammonia/methanol as deprotection reagent signi ficantly improves the synthesis of methylphosphonate-modified DNA frag ments. A mild overnight treatment at room temperature is sufficient fo r complete removal of the AMB group, whereas deprotection of conventio nally protected oligonucleotides requires much longer exposure to basi c conditions at elevated temperatures.