In Cellulo Peptide Cyclization via Gene‐Encoded Proximity‐Induced Proline‐Isothiocyanate Crosslinking
Abstract
Abstract Cyclic peptides represent a very useful modality in modern drug discovery. However, there remain substantial technical challenges in the de novo biosynthesis of complex cyclic peptides particularly in an intracellular manner. Herein, we demonstrate that an isothiocyanate (ITC) group encoded via genetic code expansion could selectively and efficiently crosslink to proximal N‐terminal Pro (P‐ITC crosslinking) and affords cyclic peptides without obvious limitations related to amino acid composition (including Lys and Cys) or sequence length. Notably via P‐ITC crosslinking, a disulfide‐bridged 13‐mer bicyclic peptide is facilely constructed in E. coli , thus lending us the ability to intracellularly construct and select complex cyclic peptides.
Article Details
Authors (8)
Zhifen Huang
State Key Laboratory of Synthetic Biology School of Life Sciences Faculty of Medicine Tianjin University Tianjin 300072 China
Shuai Jiang
State Key Laboratory of Chemical Reaction Dynamics and Dalian Coherent Light Source, Dalian Institute of Chemical Physics
Jiaying Ren
State Key Laboratory of Synthetic Biology School of Life Sciences Faculty of Medicine Tianjin University Tianjin 300072 China
Lei Zhao
School of Life Sciences, Key Laboratory of Pesticide and Chemical Biology of Ministry of Education, and Hubei Key Laboratory of Genetic Regulation and Integrative Biology, Central China Normal University
Zhuo Zhang
College of Chemistry
Hongqiang Qin
Gong Chen
State Key Laboratory and Institute of Elemento-Organic Chemistry, College of Chemistry
Weimin Xuan
State Key Laboratory of Advanced Fiber Materials & College of Chemistry and Chemical Engineering