Evaluation of Transiently O-6-Protected Guanosine Morpholino Nucleosides in Phosphorodiamidate Morpholino Oligonucleotide Synthesis

Abstract

AbstractA novel strategy is presented for the synthesis of morpholino guanosine monomers protected at O-6 with 1-(4-azidophenyl)ethan-1-ol, p-methoxybenzyl alcohol and trimethylsilylethyl groups. The introduction of these protecting groups increases the solubility of the morpholino nucleosides which is crucial during the synthesis of phosphorodiamidate morpholino oligonucleotides (PMOs). HPLC analysis shows that the trimethylsilylethyl-protected monomer gives better coupling efficiency in PMO synthesis compared to the regular monomer. Moreover the nonpolar nature of the O-6-protected monomer facilitates the preparation of guanosine-rich oligomer in solution.