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Unlocking Biomolecular Activity through Pd-Catalyzed Azides Reduction

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摘要 Comprehensive Summary Pd-mediated bioorthogonal cleavage reactions have been extensively utilized in the activation of prodrug molecules,precise regulation of protein function,and cellular engineering.However,the availability of cleavable"caging"groups is quite limited,and their application in nucleic acid modification has seldom been reported.Herein,we introduce a method based on Pd-catalyzed reduction amination of azides as a decaging strategy to activate the activity of biomolecules.We designed modifications on the bioactive sites with azides or their derivatives to mask the related biological function,followed by the release of biological activity through Pd-catalyzed NaBH4 reduction amination reaction.This study has demonstrated that the strategy can effectively be used to activate bioactive molecules such as fluorescent probes,prodrugs,and to regulate the biological function of RNA,including reverse transcription extension,binding to ligands,and cleavage activity of the CRISPR-Cas system.All results confirm that this strategy provides an efficient and controllable"OFF to ON"biological switch,capable of achieving significant regulatory effects substoichiometrically,and is expected to be extended to other biological applications.
出处 《Chinese Journal of Chemistry》 SCIE CAS CSCD 2024年第19期2305-2315,共11页 中国化学(英文版)
基金 the National Natural Science Foundation of China(Nos.22177089,21721005,92153303,22037004,22177088) the Fundamental Research Funds for the Central Universities(2042021kf0211) Translational Medicine and Interdisciplinary Research Joint Fund of Zhongnan Hospital of Wuhan University(Grant No.ZNJC202309).
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