Enzymatic Late-Stage Halogenation of Peptides.
Chembiochem
; 24(1): e202200569, 2023 01 03.
Article
en En
| MEDLINE
| ID: mdl-36259362
ABSTRACT
The late-stage site-selective derivatisation of peptides has many potential applications in structure-activity relationship studies and postsynthetic modification or conjugation of bioactive compounds. The development of orthogonal methods for C-H functionalisation is crucial for such peptide derivatisation. Among them, biocatalytic methods are increasingly attracting attention. Tryptophan halogenases emerged as valuable catalysts to functionalise tryptophan (Trp), while direct enzyme-catalysed halogenation of synthetic peptides is yet unprecedented. Here, it is reported that the Trp 6-halogenase Thal accepts a wide range of amides and peptides containing a Trp moiety. Increasing the sequence length and reaction optimisation made bromination of pentapeptides feasible with good turnovers and a broad sequence scope, while regioselectivity turned out to be sequence dependent. Comparison of X-ray single crystal structures of Thal in complex with d-Trp and a dipeptide revealed a significantly altered binding mode for the peptide. The viability of this bioorthogonal approach was exemplified by halogenation of a cyclic RGD peptide.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Triptófano
/
Halogenación
Idioma:
En
Año:
2023
Tipo del documento:
Article