半乳糖基化自牺牲连接体修饰前药型寡核苷酸的合成，可被β-半乳糖苷酶切割

Current protocols Pub Date : 2025-04-07 DOI:10.1002/cpz1.70128

Kento Miyaji, Yoshiaki Masaki, Kohji Seio

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引用次数: 0

摘要

本方案描述了通过在o4位置的自溶连接体制备与半乳糖偶联的修饰胸腺嘧啶的过程，以及合成含有这些修饰胸腺嘧啶的β-半乳糖苷酶响应的前药型寡脱氧核苷酸（ONs）的过程。这些前体药物- on被设计为响应β-半乳糖苷酶而被激活，从而在特定细胞或组织中实现靶向激活，并可能有助于减少不良反应。©2025 Wiley期刊有限公司基本方案1:o4修饰胸苷磷酸酯的制备基本方案2:o4修饰胸苷磷酸酯的制备支持方案1：三唑基胸苷衍生物的制备支持方案2：苯甲醇衍生物的制备基本方案3:β-半乳糖苷酶反应性ODNs 1至5的制备

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Synthesis of Prodrug-Type Oligonucleotides Modified With a Galactosylated Self-Immolative Linker Cleavable by β-Galactosidase

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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