Synthesis and Biophysical Properties of Triazole-Incorporated PMOs (TzPMOs): A Convergent, Click Ligation Approach.
J Org Chem
; 89(5): 2895-2903, 2024 03 01.
Article
em En
| MEDLINE
| ID: mdl-38344977
ABSTRACT
The synthesis of phosphorodiamidate morpholino oligonucleotides (PMOs) incorporating single or double triazole rings in the backbone has been achieved via Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC). The synthetic approach implemented is fundamentally convergent, involving the ligation of a 5'-azide PMO fragment to a 3'-alkyne fragment both in solution and on solid support. To access the 3'-alkyne PMO fragment, we synthesized 3'-N-propargyl chlorophosphoramidate morpholino monomers for all four nucleobases. The resulting triazole-incorporated PMOs (TzPMOs) have exhibited comparable or improved binding affinity toward complementary deoxyribonucleic acid (DNA)/ribonucleic acid (RNA) strands compared to its regular analogues. Finally, a full-length TzPMO was designed to target the Nanog gene, demonstrating almost identical hybridization properties when compared to its regular version. Circular dichroism studies revealed a B-type helical conformation for the duplexes formed by TzPMOs.
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Base de dados:
MEDLINE
Assunto principal:
Azidas
/
Alcinos
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article