Beilstein J. Org. Chem.2018,14, 436–469, doi:10.3762/bjoc.14.32
group; oligonucleotide prodrugs; reduction-responsive; stimuli-responsive nucleic acids; thermolytic prodrugs; Introduction
For past decades, oligonucleotide-based therapies have been widely developed using short synthetic oligonucleotides (ONs) and their chemically modified mimics as powerful tools to
subject was thoroughly documented.
Review
Reduction-responsive ONs
These modified ONs are responsive to the reducing environment inside cells due to the natural presence of glutathione (GSH) as a conversion trigger. ONs that are responsive to the action of reductases under hypoxic conditions will be
intracellular abundant GSH. In this context, two classes of reduction-responsive units, disulfide-bond and benzyl-containing groups, were mainly introduced in prodrug-based ONs.
Modifications at the internucleotide linkage
Masking the negative charges of native phosphates typically improves cell penetration of
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Graphical Abstract
Scheme 1:
Demasking under reducing agents of ON prodrugs modified as phosphotriesters with A) benzyl groups [13] ...