Fig. 1: Automated fast-flow technology can produce on-demand customized PMO sequences.
From: Fully automated fast-flow synthesis of antisense phosphorodiamidate morpholino oligomers
a The structure of PMO drug Golodirsen is shown. b Each nucleotide is incorporated as a trityl-protected phosphoramido chloridate in 1,3-dimethyl-2-imidazolidinone (DMI). Detritylation frees the 3′-terminal amine with the conjugate acid of a non-nucleophilic heterocycle, typically 4-cyanopyridine in dichloromethane–trifluoroethanol (DCM/TFE) mixtures. Neutralization of the 3′-amine prepares the chain for the next coupling reaction using tertiary amines in DCM/isopropanol mixtures. c Development of PMO drugs requires testing of many sequences and laborious production of sequential revisions. An automated fast-flow synthesizer allows for rapid manufacture of PMO sequences at 90 °C.
