Oxidative cyclization reagents reveal tryptophan cation-π interactions.
In: Nature, Jg. 627 (2024-03-01), Heft 8004, S. 680-687
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Zugriff:
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.)
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Oxidative cyclization reagents reveal tryptophan cation-π interactions.
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Autor/in / Beteiligte Person: | Xie, X ; Moon, PJ ; Crossley, SWM ; Bischoff, AJ ; He, D ; Li, G ; Dao, N ; Gonzalez-Valero, A ; Reeves, AG ; McKenna, JM ; Elledge, SK ; Wells, JA ; Toste, FD ; Chang, CJ |
Zeitschrift: | Nature, Jg. 627 (2024-03-01), Heft 8004, S. 680-687 |
Veröffentlichung: | Basingstoke : Nature Publishing Group ; <i>Original Publication</i>: London, Macmillan Journals ltd., 2024 |
Medientyp: | academicJournal |
ISSN: | 1476-4687 (electronic) |
DOI: | 10.1038/s41586-024-07140-6 |
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