Oxidative cyclization reagents reveal tryptophan cation-π interactions.
Nature
; 627(8004): 680-687, 2024 Mar.
Article
em En
| MEDLINE
| ID: mdl-38448587
ABSTRACT
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 proteomics1-3. Owing to their high nucleophilicity, cysteine and lysine residues are the most common points of attachment for protein bioconjugation chemistry through acid-base reactivity3,4. 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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Triptofano
/
Proteínas
/
Cátions
/
Ciclização
/
Indicadores e Reagentes
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article