{"title":"Tuning Tetrazine Substituents to Enhance Vinyltetrazine Labeling Performance.","authors":"Haoxing Wu, Xinxin Liang, Jie Li, Xirui Liu, Xinyu He, Tingyu Chen, Shiyi Zhou","doi":"10.1002/cbic.202500067","DOIUrl":null,"url":null,"abstract":"<p><p>The site-specific labelling of peptides and proteins is a powerful tool for investigating biological processes. We demonstrated that the powerful thiol-specific labelling reagent vinyltetrazine activates pro-drugs and enables 18F and near-infrared dual-modality imaging. We predicted that substitutions at the 3-position of tetrazine could affect the labelling efficiency, bioorthogonal kinetics, and stability. Six vinyltetrazines with different 3-position modifications exhibited rapid labelling, and subsequently, bioorthogonal kinetics and excellent stability. Vinyltetrazine labelling modified the charge characteristics and lipophilicity of target peptides, thereby improving cellular uptake. This research on tuning tetrazine substituents will aid in the construction of a comprehensive vinyltetrazine library, leading to the development of new peptide conjugates and pre-targeted immuno-positron emission tomography (immune-PET) imaging.</p>","PeriodicalId":140,"journal":{"name":"ChemBioChem","volume":" ","pages":"e202500067"},"PeriodicalIF":2.6000,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"ChemBioChem","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1002/cbic.202500067","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
The site-specific labelling of peptides and proteins is a powerful tool for investigating biological processes. We demonstrated that the powerful thiol-specific labelling reagent vinyltetrazine activates pro-drugs and enables 18F and near-infrared dual-modality imaging. We predicted that substitutions at the 3-position of tetrazine could affect the labelling efficiency, bioorthogonal kinetics, and stability. Six vinyltetrazines with different 3-position modifications exhibited rapid labelling, and subsequently, bioorthogonal kinetics and excellent stability. Vinyltetrazine labelling modified the charge characteristics and lipophilicity of target peptides, thereby improving cellular uptake. This research on tuning tetrazine substituents will aid in the construction of a comprehensive vinyltetrazine library, leading to the development of new peptide conjugates and pre-targeted immuno-positron emission tomography (immune-PET) imaging.
期刊介绍：
ChemBioChem (Impact Factor 2018: 2.641) publishes important breakthroughs across all areas at the interface of chemistry and biology, including the fields of chemical biology, bioorganic chemistry, bioinorganic chemistry, synthetic biology, biocatalysis, bionanotechnology, and biomaterials. It is published on behalf of Chemistry Europe, an association of 16 European chemical societies, and supported by the Asian Chemical Editorial Society (ACES).
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