Journal
CHEMICAL SCIENCE
Volume 8, Issue 9, Pages 6577-6582Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c7sc02686b
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Funding
- 863 Program [2015AA020941]
- National Key Research Project [2015CB910300]
- National Natural Science Foundation of China [21474003, 91427304, 21633001]
- 1000 Plan (Youth)
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Genetically encoded covalent peptide tagging technology, such as the SpyTag-SpyCatcher reaction, has emerged as a unique way to do chemistry with proteins. Herein, we report the reactivity engineering of SpyTag-SpyCatcher mutant pairs and show that distinct reactivity can be encrypted for the same reaction based on protein sequences of high similarity. Valuable features, including high selectivity, inverse temperature dependence and (nearly) orthogonal reactivity, could be achieved based on as few as three mutations. This demonstrates the robustness of the SpyTag-SpyCatcher reaction and the plasticity of its sequence specificity, pointing to a family of engineered protein chemistry tools.
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