A Genetically Encoded, Phage-Displayed Cyclic-Peptide Library.
Angew Chem Int Ed Engl
; 58(44): 15904-15909, 2019 10 28.
Article
en En
| MEDLINE
| ID: mdl-31398275
ABSTRACT
Superior to linear peptides in biological activities, cyclic peptides are considered to have great potential as therapeutic agents. To identify cyclic-peptide ligands for therapeutic targets, phage-displayed peptide libraries in which cyclization is achieved by the covalent conjugation of cysteines have been widely used. To resolve drawbacks related to cysteine conjugation, we have invented a phage-display technique in which its displayed peptides are cyclized through a proximity-driven Michael addition reaction between a cysteine and an amber-codon-encoded Nϵ -acryloyl-lysine (AcrK). Using a randomized 6-mer library in which peptides were cyclized at two ends through a cysteine-AcrK linker, we demonstrated the successful selection of potent ligands for TEV protease and HDAC8. All selected cyclic peptide ligands showed 4- to 6-fold stronger affinity to their protein targets than their linear counterparts. We believe this approach will find broad applications in drug discovery.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Péptidos Cíclicos
/
Biblioteca de Péptidos
/
Código Genético
Tipo de estudio:
Clinical_trials
Límite:
Humans
Idioma:
En
Revista:
Angew Chem Int Ed Engl
Año:
2019
Tipo del documento:
Article
País de afiliación:
Estados Unidos