Protein-Templated Peptide Ligation

• Published in: Angewandte Chemie International Edition 2014-04, Vol.53 (17), p.4337-4340
• Main Authors: Brauckhoff, Nicolas, Hahne, Gernot, Yeh, Johannes T.-H., Grossmann, Tom N.
• Format: Article
• Language: English
• Subjects: bioorthogonal reactions; CREB-Binding Protein - metabolism; HSP70 Heat-Shock Proteins - chemistry; HSP70 Heat-Shock Proteins - metabolism; Humans; Labels; Linkages; Magnetic Resonance Spectroscopy; Molecular Structure; Myeloid-Lymphoid Leukemia Protein - metabolism; Nucleic acids; Peptide Fragments - metabolism; peptide ligation; Peptides; Protein Conformation; Protein Interaction Domains and Motifs; protein modification; Proteins; Robustness; solid-phase peptide synthesis; templated reactions
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201400681

Molecular templates bind particular reactants, thereby increasing their effective concentrations and accelerating the corresponding reaction. This concept has been successfully applied to a number of chemical problems with a strong focus on nucleic acid templated reactions. We present the first protein‐templated reaction that allows N‐terminal linkage of two peptides. In the presence of a protein template, ligation reactions were accelerated by more than three orders of magnitude. The templated reaction is highly selective and proved its robustness in a protein‐labeling reaction that was performed in crude cell lysate. Come together: A protein template was used to mediate the ligation reaction between two peptides which were equipped with suitable electrophilic and nucleophilic groups. These templated reactions were accelerated by more than three orders of magnitude relative to the nontemplated reactions and proved to be highly selective when used to label proteins within crude cell lysate.