Covalently Engineered Nanobody Chimeras for Targeted Membrane Protein Degradation.
J Am Chem Soc
; 143(40): 16377-16382, 2021 10 13.
Article
em En
| MEDLINE
| ID: mdl-34596400
ABSTRACT
The targeted degradation of membrane proteins would afford an attractive and general strategy for treating various diseases that remain difficult with the current proteolysis-targeting chimera (PROTAC) methodology. We herein report a covalent nanobody-based PROTAC strategy, termed GlueTAC, for targeted membrane protein degradation with high specificity and efficiency. We first established a mass-spectrometry-based screening platform for the rapid development of a covalent nanobody (GlueBody) that allowed proximity-enabled cross-linking with surface antigens on cancer cells. By conjugation with a cell-penetrating peptide and a lysosomal-sorting sequence, the resulting GlueTAC chimera triggered the internalization and degradation of programmed death-ligand 1 (PD-L1), which provides a new avenue to target and degrade cell-surface proteins.
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
Base de dados:
MEDLINE
Assunto principal:
Proteólise
Idioma:
En
Revista:
J Am Chem Soc
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
China