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Improved variants of SrtA for site-specific conjugation on antibodies and proteins with high efficiency
Chen, Long ; Cohen, Justin ; Song, Xiaoda ; Zhao, Aishan ; Ye, Zi ; Feulner, Christine J. ; Doonan, Patrick ; Somers, Will ; Lin, Laura ; Chen, Peng R.
刊名SCIENTIFIC REPORTS
2016
关键词UNNATURAL AMINO-ACIDS MONOCLONAL-ANTIBODY STAPHYLOCOCCUS-AUREUS DRUG CONJUGATION CYTOTOXIC DRUG SORTASE TRANSGLUTAMINASE IDENTIFICATION CHEMISTRY RESIDUES
DOI10.1038/srep31899
英文摘要Sortase mediated ligation is a highly specific platform for conjugation that relies on the specificity of the transpeptidase Sortase A ( SrtA) for short peptide sequences ( LPXTG and GGG). SrtA retains its specificity while accepting a wide range of potential substrates, but its broad use is limited by the wild-type enzyme's poor kinetics, which require large amounts of SrtA and extended reaction times for efficient conjugation. Prior explorations have aimed to improve the kinetics of SrtA with limited success. Herein we describe the discovery of further improved SrtA variants with increased efficiency for the conjugation reaction, and demonstrate their robustness in labelling proteins and antibodies in a site-specific manner. Our variants require significantly lower amounts of enzyme than WT SrtA and can be used to attach small molecules to the N or C-terminus of the heavy or light chain in antibodies with excellent yields. These improved variants can also be used for highly efficient site-specific PEGylation.; SCI(E); PubMed; ARTICLE; Laura.Lin@pfizer.com; pengchen@pku.edu.cn; 31899; 6
语种英语
内容类型期刊论文
源URL[http://ir.pku.edu.cn/handle/20.500.11897/491568]  
专题化学与分子工程学院
推荐引用方式
GB/T 7714
Chen, Long,Cohen, Justin,Song, Xiaoda,et al. Improved variants of SrtA for site-specific conjugation on antibodies and proteins with high efficiency[J]. SCIENTIFIC REPORTS,2016.
APA Chen, Long.,Cohen, Justin.,Song, Xiaoda.,Zhao, Aishan.,Ye, Zi.,...&Chen, Peng R..(2016).Improved variants of SrtA for site-specific conjugation on antibodies and proteins with high efficiency.SCIENTIFIC REPORTS.
MLA Chen, Long,et al."Improved variants of SrtA for site-specific conjugation on antibodies and proteins with high efficiency".SCIENTIFIC REPORTS (2016).
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