Thiophosphoramidate morpholino (TMO) and their DNA chimeras (TMO-DNA) were prepared on DNA synthesizers using phosphoramidite chemistry. These new oligonucleotide analogs contained morpholino- and 2’-deoxyribonucleosides joined through thiophosphor/phosphor internucleotide linkages and were prepared from synthons having standard amide protection on the nucleoside bases. The TMO and TMO-DNA chimeras were observed to have higher melting temperatures when compared to natural DNA/DNA and DNA/RNA duplexes. Moreover the TMO/RNA duplexes exhibit the A-form structure and are RNase H1 active. Treatment of HeLa cells with fluorescently labeled TMO and TMO-DNA chimeras demonstrated that these analogues were efficiently taken up by cells in the absence of a lipid transfection reagent and stimulated biological activity in a dual luciferase assay. Because of the simplistic synthesis procedures, various TMO analogues are now readily available and should therefore open new pathways for research into the antisense and diagnostic oligonucleotide fields.

Thiophosphoramidate morpholino: A new class of antisense oligonucleotides

254th National Meeting (2017)

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