Collapsed Star Copolymers Exhibiting Near Perfect Mimicry of the Therapeutic Protein "TRAIL".
J Am Chem Soc
; 146(31): 22093-22102, 2024 Aug 07.
Article
em En
| MEDLINE
| ID: mdl-39054926
ABSTRACT
Here we introduce amphiphilic star polymers as versatile protein mimics capable of approximating the activity of certain native proteins. Our study focuses on designing a synthetic polymer capable of replicating the biological activity of TRAIL, a promising anticancer protein that shows very poor circulation half-life. Successful protein mimicry requires precise control over the presentation of receptor-binding peptides from the periphery of the polymer scaffold while maintaining enough flexibility for protein-peptide binding. We show that this can be achieved by building hydrophobic blocks into the core of a star-shaped polymer, which drives unimolecular collapse in water. By screening a library of diblock copolymer stars, we were able to design structures with IC50's of â¼4 nM against a colon cancer cell line (COLO205), closely approximating the activity of the native TRAIL protein. This finding highlights the broad potential for simple synthetic polymers to mimic the biological activity of complex proteins.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Polímeros
Limite:
Humans
Idioma:
En
Revista:
J Am Chem Soc
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Austrália