Synthesis of Prodrug-Type Oligonucleotides Modified With a Galactosylated Self-Immolative Linker Cleavable by
Kento Miyaji1, Yoshiaki Masaki1,2, Kohji Seio1
1School of Life Science and Technology, Institute of Science Tokyo, Kanagawa, Japan.
Abstract:
This protocol describes procedures for the preparation of a modified thymidine conjugated with galactose via a self-immolative linker at the O4-position, and the synthesis of β-galactosidase-responsive prodrug-type oligodeoxynucleotides (ONs) containing these modified thymidines. These prodrug-ONs are designed to be activated in response to β-galactosidase, enabling targeted activation in specific cells or tissues and potentially contributing to the reduction of adverse effects. © 2025 Wiley Periodicals LLC. Basic Protocol 1: Preparation of O4-modified thymidine phosphoramidite 7 Basic Protocol 2: Preparation of O4-modified thymidine phosphoramidite 15 Support Protocol 1: Preparation of triazolyl thymidine derivative 1 Support Protocol 2: Preparation of benzyl alcohol derivative 2 Basic Protocol 3: Preparation of β-galactosidase-responsive ODNs 1 to 5.
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