{"title":"Synthesis of Prodrug-Type Oligonucleotides Modified With a Galactosylated Self-Immolative Linker Cleavable by β-Galactosidase","authors":"Kento Miyaji, Yoshiaki Masaki, Kohji Seio","doi":"10.1002/cpz1.70128","DOIUrl":null,"url":null,"abstract":"<p>This protocol describes procedures for the preparation of a modified thymidine conjugated with galactose via a self-immolative linker at the <i>O</i>4-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.</p><p><b>Basic Protocol 1</b>: Preparation of <i>O</i>4-modified thymidine phosphoramidite <b>7</b></p><p><b>Basic Protocol 2</b>: Preparation of <i>O</i>4-modified thymidine phosphoramidite <b>15</b></p><p><b>Support Protocol 1</b>: Preparation of triazolyl thymidine derivative <b>1</b></p><p><b>Support Protocol 2</b>: Preparation of benzyl alcohol derivative <b>2</b></p><p><b>Basic Protocol 3</b>: Preparation of β-galactosidase-responsive <b>ODNs 1</b> to <b>5</b></p>","PeriodicalId":93970,"journal":{"name":"Current protocols","volume":"5 4","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current protocols","FirstCategoryId":"1085","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/cpz1.70128","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
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
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
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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