Streamlined Chemoenzymatic Synthesis of Cyclic Peptides by Non-ribosomal Peptide Cyclases.
J Am Chem Soc
; 145(6): 3270-3275, 2023 02 15.
Article
em En
| MEDLINE
| ID: mdl-36638272
ABSTRACT
Macrocyclization improves the pharmaceutical properties of peptides; however, regio- and chemoselective intramolecular cyclizations remain challenging. Here we developed a streamlined chemoenzymatic approach to synthesize cyclic peptides by exploiting non-ribosomal peptide (NRP) cyclases. Linear peptides linked to the resin through a C-terminal diol ester functionality are synthesized on a solid support, to circumvent the installation of leaving groups to the peptidic substrates in the liquid phase which often triggers undesirable epimerization. Cleavage of the resin-bound peptides yielded the diol esters with sufficient purity to be readily cyclized in a head-to-tail manner by SurE, a representative penicillin-binding protein-type thioesterase (PBP-type TE). Explorations of homologous wild-type enzymes as well as rational protein engineering have broadened the scope of the enzymatic macrolactamization. This method will potentially accelerate the exploitation of NRP cyclases as biocatalysts.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Peptídeos
/
Peptídeos Cíclicos
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article