Fiche du document
20 mars 2016
- doi: 10.1021/acschembio.5b00963
- issn: 1554-8929
Ce document est lié à :
info:eu-repo/semantics/altIdentifier/doi/10.1021/acschembio.5b00963
Ce document est lié à :
info:eu-repo/semantics/altIdentifier/pmid/26929989
Ce document est lié à :
info:eu-repo/semantics/altIdentifier/eissn/1554-8937
Ce document est lié à :
info:eu-repo/semantics/altIdentifier/urn/urn:nbn:ch:serval-BIB_0A65DEA929783
info:eu-repo/semantics/openAccess , Copying allowed only for non-profit organizations , https://serval.unil.ch/disclaimer
Sujets proches
Military strategy ProteidsCiter ce document
P. Diderich et al., « Phage Selection of Chemically Stabilized α-Helical Peptide Ligands. », Serveur académique Lausannois, ID : 10.1021/acschembio.5b00963
Métriques
Partage / Export
Résumé
Short α-helical peptides stabilized by linkages between constituent amino acids offer an attractive format for ligand development. In recent years, a range of excellent ligands based on stabilized α-helices were generated by rational design using α-helical peptides of natural proteins as templates. Herein, we developed a method to engineer chemically stabilized α-helical ligands in a combinatorial fashion. In brief, peptides containing cysteines in position i and i + 4 are genetically encoded by phage display, the cysteines are modified with chemical bridges to impose α-helical conformations, and binders are isolated by affinity selection. We applied the strategy to affinity mature an α-helical peptide binding β-catenin. We succeeded in developing ligands with Kd's as low as 5.2 nM, having >200-fold improved affinity. The strategy is generally applicable for affinity maturation of any α-helical peptide. Compared to hydrocarbon stapled peptides, the herein evolved thioether-bridged peptide ligands can be synthesized more easily, as no unnatural amino acids are required and the cyclization reaction is more efficient and yields no stereoisomers. A further advantage of the thioether-bridged peptide ligands is that they can be expressed recombinantly as fusion proteins.