{"title":"用于 PROTAC 的基于三唑的单锅光催化连接技术","authors":"","doi":"10.1016/j.xcrp.2024.102139","DOIUrl":null,"url":null,"abstract":"<p>Proteolysis-targeting chimeras (PROTACs) are a powerful approach for targeted protein degradation. One of the current bottlenecks for developing PROTACs is the lack of an operationally simple linkerology to rapidly construct PROTACs with various linkers. The classic convergent synthesis strategy by coupling pre-assembled linkers with two ligands stepwise commonly needs at least four steps to give the final target PROTACs, which results in low total yields with long reaction times (several days) and tedious operations. Here, we develop an efficient photocatalytic one-pot linkerology for the rapid coupling of analogs of PROTACs containing triazole-based linkers without any linker-pre-assembled procedure. The reaction was completed within 4 h with up to 95% yields at room temperature. Easily accessible cyclic ethers are directly used as linker precursors to furnish the one-pot fashion, including alkenyl, polyethylene glycol (PEG), ketone, and cyclohexane chains. The study provides a highly efficient, step-economic, operationally simple, and environmentally friendly one-pot linkerology for PROTAC drug discovery.</p>","PeriodicalId":9703,"journal":{"name":"Cell Reports Physical Science","volume":"57 1","pages":""},"PeriodicalIF":7.9000,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"A one-pot photocatalytic triazole-based linkerology for PROTACs\",\"authors\":\"\",\"doi\":\"10.1016/j.xcrp.2024.102139\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Proteolysis-targeting chimeras (PROTACs) are a powerful approach for targeted protein degradation. One of the current bottlenecks for developing PROTACs is the lack of an operationally simple linkerology to rapidly construct PROTACs with various linkers. The classic convergent synthesis strategy by coupling pre-assembled linkers with two ligands stepwise commonly needs at least four steps to give the final target PROTACs, which results in low total yields with long reaction times (several days) and tedious operations. Here, we develop an efficient photocatalytic one-pot linkerology for the rapid coupling of analogs of PROTACs containing triazole-based linkers without any linker-pre-assembled procedure. The reaction was completed within 4 h with up to 95% yields at room temperature. Easily accessible cyclic ethers are directly used as linker precursors to furnish the one-pot fashion, including alkenyl, polyethylene glycol (PEG), ketone, and cyclohexane chains. The study provides a highly efficient, step-economic, operationally simple, and environmentally friendly one-pot linkerology for PROTAC drug discovery.</p>\",\"PeriodicalId\":9703,\"journal\":{\"name\":\"Cell Reports Physical Science\",\"volume\":\"57 1\",\"pages\":\"\"},\"PeriodicalIF\":7.9000,\"publicationDate\":\"2024-08-02\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cell Reports Physical Science\",\"FirstCategoryId\":\"103\",\"ListUrlMain\":\"https://doi.org/10.1016/j.xcrp.2024.102139\",\"RegionNum\":2,\"RegionCategory\":\"综合性期刊\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell Reports Physical Science","FirstCategoryId":"103","ListUrlMain":"https://doi.org/10.1016/j.xcrp.2024.102139","RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
A one-pot photocatalytic triazole-based linkerology for PROTACs
Proteolysis-targeting chimeras (PROTACs) are a powerful approach for targeted protein degradation. One of the current bottlenecks for developing PROTACs is the lack of an operationally simple linkerology to rapidly construct PROTACs with various linkers. The classic convergent synthesis strategy by coupling pre-assembled linkers with two ligands stepwise commonly needs at least four steps to give the final target PROTACs, which results in low total yields with long reaction times (several days) and tedious operations. Here, we develop an efficient photocatalytic one-pot linkerology for the rapid coupling of analogs of PROTACs containing triazole-based linkers without any linker-pre-assembled procedure. The reaction was completed within 4 h with up to 95% yields at room temperature. Easily accessible cyclic ethers are directly used as linker precursors to furnish the one-pot fashion, including alkenyl, polyethylene glycol (PEG), ketone, and cyclohexane chains. The study provides a highly efficient, step-economic, operationally simple, and environmentally friendly one-pot linkerology for PROTAC drug discovery.
期刊介绍:
Cell Reports Physical Science, a premium open-access journal from Cell Press, features high-quality, cutting-edge research spanning the physical sciences. It serves as an open forum fostering collaboration among physical scientists while championing open science principles. Published works must signify significant advancements in fundamental insight or technological applications within fields such as chemistry, physics, materials science, energy science, engineering, and related interdisciplinary studies. In addition to longer articles, the journal considers impactful short-form reports and short reviews covering recent literature in emerging fields. Continually adapting to the evolving open science landscape, the journal reviews its policies to align with community consensus and best practices.