A Macrocyclic Peptide Library with a Structurally Constrained Cyclopropane-containing Building Block Leads to Thiol-independent Inhibitors of Phosphoglycerate Mutase.
Chem Asian J
; 15(17): 2631-2636, 2020 Sep 01.
Article
em En
| MEDLINE
| ID: mdl-32633882
ABSTRACT
Here we report the construction of an mRNA-encoded library of thioether-closed macrocyclic peptides by using an N-chloroacetyl-cyclopropane-containing exotic initiator whose structure is more constrained than the ordinary N-chloroacetyl-α-amino acid initiators. The use of such an initiator has led to a macrocycle library with significantly suppressed population of lariat-shaped species compared with the conventional libraries. We previously used a conventional library and identified a small lariat thioether-macrocycle with a tail peptide with a C-terminal free Cys whose sidechain plays an essential role in potent inhibitory activity against a parasitic model enzyme, phosphoglycerate mutase. On the other hand, the cyclopropane-containing macrocycle library has yielded a larger thioether-macrocycle lacking a free Cys residue, which exhibits potent inhibitory activity to the same enzyme with a different mode of action. This result indicates that such a cyclopropane-containing macrocycle library would allow us to access mechanistically distinct macrocycles.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Peptídeos
/
Compostos de Sulfidrila
/
Fosfoglicerato Mutase
/
Biblioteca de Peptídeos
/
Ciclopropanos
/
Compostos Macrocíclicos
/
Inibidores Enzimáticos
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article