Proximity-driven site-specific cyclization of phage-displayed peptides.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
24 Aug 2024
24 Aug 2024
Historique:
received:
17
11
2023
accepted:
13
08
2024
medline:
26
8
2024
pubmed:
26
8
2024
entrez:
24
8
2024
Statut:
epublish
Résumé
Cyclization provides a general strategy for improving the proteolytic stability, cell membrane permeability and target binding affinity of peptides. Insertion of a stable, non-reducible linker into a disulphide bond is a commonly used approach for cyclizing phage-displayed peptides. However, among the vast collection of cysteine reactive linkers available, few provide the selectivity required to target specific cysteine residues within the peptide in the phage display system, whilst sparing those on the phage capsid. Here, we report the development of a cyclopropenone-based proximity-driven chemical linker that can efficiently cyclize synthetic peptides and peptides fused to a phage-coat protein, and cyclize phage-displayed peptides in a site-specific manner, with no disruption to phage infectivity. Our cyclization strategy enables the construction of stable, highly diverse phage display libraries. These libraries can be used for the selection of high-affinity cyclic peptide binders, as exemplified through model selections on streptavidin and the therapeutic target αvβ3.
Identifiants
pubmed: 39181880
doi: 10.1038/s41467-024-51610-4
pii: 10.1038/s41467-024-51610-4
doi:
Substances chimiques
Peptide Library
0
Peptides, Cyclic
0
Streptavidin
9013-20-1
Capsid Proteins
0
Cysteine
K848JZ4886
Cyclopropanes
0
Peptides
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
7308Subventions
Organisme : RCUK | Biotechnology and Biological Sciences Research Council (BBSRC)
ID : 10046039
Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)
ID : 493006134
Informations de copyright
© 2024. The Author(s).
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