Oxidative cyclization reagents reveal tryptophan cation-π interactions.

Autor: Xie X; Department of Chemistry, University of California, Berkeley, Berkeley, CA, USA.; California Institute for Quantitative Biosciences, University of California, Berkeley, Berkeley, CA, USA.; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA., Moon PJ; Department of Chemistry, University of California, Berkeley, Berkeley, CA, USA., Crossley SWM; Department of Chemistry, University of California, Berkeley, Berkeley, CA, USA., Bischoff AJ; Department of Chemistry, University of California, Berkeley, Berkeley, CA, USA.; Molecular Biophysics and Integrated Bioimaging Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA., He D; Department of Chemistry, University of California, Berkeley, Berkeley, CA, USA.; California Institute for Quantitative Biosciences, University of California, Berkeley, Berkeley, CA, USA.; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA., Li G; Department of Chemistry, University of California, Berkeley, Berkeley, CA, USA., Dao N; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA., Gonzalez-Valero A; Department of Chemistry, University of California, Berkeley, Berkeley, CA, USA., Reeves AG; Department of Chemistry, University of California, Berkeley, Berkeley, CA, USA., McKenna JM; Novartis Institutes of Biomedical Research, Cambridge, MA, USA., Elledge SK; Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA, USA., Wells JA; Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA, USA.; Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, CA, USA., Toste FD; Department of Chemistry, University of California, Berkeley, Berkeley, CA, USA. fdtoste@berkeley.edu., Chang CJ; Department of Chemistry, University of California, Berkeley, Berkeley, CA, USA. chrischang@berkeley.edu.; California Institute for Quantitative Biosciences, University of California, Berkeley, Berkeley, CA, USA. chrischang@berkeley.edu.; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA. chrischang@berkeley.edu.
Jazyk: angličtina
Zdroj: Nature [Nature] 2024 Mar; Vol. 627 (8004), pp. 680-687. Date of Electronic Publication: 2024 Mar 06.
DOI: 10.1038/s41586-024-07140-6
Abstrakt: Methods for selective covalent modification of amino acids on proteins can enable a diverse array of applications, spanning probes and modulators of protein function to proteomics 1-3 . Owing to their high nucleophilicity, cysteine and lysine residues are the most common points of attachment for protein bioconjugation chemistry through acid-base reactivity 3,4 . Here we report a redox-based strategy for bioconjugation of tryptophan, the rarest amino acid, using oxaziridine reagents that mimic oxidative cyclization reactions in indole-based alkaloid biosynthetic pathways to achieve highly efficient and specific tryptophan labelling. We establish the broad use of this method, termed tryptophan chemical ligation by cyclization (Trp-CLiC), for selectively appending payloads to tryptophan residues on peptides and proteins with reaction rates that rival traditional click reactions and enabling global profiling of hyper-reactive tryptophan sites across whole proteomes. Notably, these reagents reveal a systematic map of tryptophan residues that participate in cation-π interactions, including functional sites that can regulate protein-mediated phase-separation processes.
(© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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