Bicyclic peptide ligands pulled out of cysteine-rich peptide libraries.
J Am Chem Soc
; 135(17): 6562-9, 2013 May 01.
Article
em En
| MEDLINE
| ID: mdl-23560397
ABSTRACT
Bicyclic peptide ligands were found to have good binding affinity and target specificity. However, the method applied to generate bicyclic ligands based on phage-peptide alkylation is technically complex and limits its application to specialized laboratories. Herein, we report a method that involves a simpler and more robust procedure that additionally allows screening of structurally more diverse bicyclic peptide libraries. In brief, phage-encoded combinatorial peptide libraries of the format X(m)CX(n)CX(o)CX(p) are oxidized to connect two pairs of cysteines (C). This allows the generation of 3 × (m + n + o + p) different peptide topologies because the fourth cysteine can appear in any of the (m + n + o + p) randomized amino acid positions (X). Panning of such libraries enriched strongly peptides with four cysteines and yielded tight binders to protein targets. X-ray structure analysis revealed an important structural role of the disulfide bridges. In summary, the presented approach offers facile access to bicyclic peptide ligands with good binding affinities.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Peptídeos
/
Compostos Bicíclicos com Pontes
/
Cisteína
Tipo de estudo:
Clinical_trials
Idioma:
En
Revista:
J Am Chem Soc
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Suíça