ArticleAngewandte Chemie (International ed. in English)2018
In Situ Cyclization of Native Proteins: Structure-Based Design of a Bicyclic Enzyme.
Article in Angewandte Chemie (International ed. in English), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed.
- Chemical reactions for the ligand-directed modification of native proteins.Chemical Society reviews · 2026Review
- Multiple aspartic proteases process PE and PPE proteins on the mycobacterial surface of pathogenic mycobacteria.The Journal of biological chemistry · 2026Article
- Multicyclic D-Stereospecific Hydrolase Dimer With High Sustained Activity.Angewandte Chemie (International ed. in English) · 2026Article
- Advancing protein engineering via organic chemistry.Communications chemistry · 2026Review
- Folded-state compatibility and unfolded-state constraint govern staple-based stabilization: guidelines from a coiled-coil model.RSC chemical biology · 2026Article
- Helicity-Dependent Enzymatic Peptide Cyclization.Journal of peptide science : an official publication of the European Peptide Society · 2025Article
- Article
- Bicyclic Engineered Sortase A Performs Transpeptidation under Denaturing Conditions.Bioconjugate chemistry · 2023Article
- Peptide-based covalent inhibitors of protein-protein interactions.Journal of peptide science : an official publication of the European Peptide Society · 2023Review
- Structural guidelines for stabilization of α-helical coiled coilsRSC chemical biology · 2022Article
- Tuning Enzyme Thermostability via Computationally Guided Covalent Stapling and Structural Basis of Enhanced Stabilization.Biochemistry · 2022Article
- Challenges in the use of sortase and other peptide ligases for site-specific protein modification.Chemical Society reviews · 2022Review
- Unprotected peptide macrocyclization and stapling via a fluorine-thiol displacement reaction.Nature communications · 2022Article
- Protein Macrocyclization for Tertiary Structure Stabilization.Chembiochem : a European journal of chemical biology · 2021Review
- Article
- Enhancing Robustness of Sortase A by Loop Engineering and Backbone Cyclization.Chemistry (Weinheim an der Bergstrasse, Germany) · 2020Article
- Long-range PEG Stapling: Macrocyclization for Increased Protein Conformational Stability and Resistance to Proteolysis.RSC chemical biology · 2020Article
- Engineered peptide ligases for cell signaling and bioconjugation.Biochemical Society transactions · 2020Review
- In Situ Cyclization of Proteins (INCYPRO): Cross-Link Derivatization Modulates Protein Stability.The Journal of organic chemistry · 2020Article
- Vinylphosphonites for Staudinger-induced chemoselective peptide cyclization and functionalization.Chemical science · 2019Article
Corrections and comments
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Increased tolerance of enzymes towards thermal and chemical stress is required for many applications and can be achieved by macrocyclization of the enzyme resulting in the stabilizing of its tertiary structure. Thus far, macrocyclization approaches utilize a very limited structural diversity, which complicates the design process. Herein, we report an approach that enables cyclization through the installation of modular crosslinks into native proteins composed entirely of proteinogenic amino acids. Our stabilization procedure involves the introduction of three surface-exposed cysteine residues, which are reacted with a triselectrophile, resulting in the in situ cyclization of the protein (INCYPRO). A bicyclic version of sortase A was designed that exhibits increased tolerance towards thermal as well as chemical denaturation, and proved to be efficient in protein labeling under denaturing conditions. In addition, we applied INCYPRO to the KIX domain, resulting in up to 24 °C increased thermal stability.
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Registered trials
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