8ad8

Publication Abstract from PubMed

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.

Enzymatic Late-Stage Halogenation of Peptides.,Schnepel C, Moritzer AC, Gafe S, Montua N, Minges H, Niess A, Niemann HH, Sewald N Chembiochem. 2022 Oct 19. doi: 10.1002/cbic.202200569. PMID:36259362^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.