C-terminal modification and functionalization of proteins via a self-cleavage tag triggered by a small molecule.
Nat Commun
; 14(1): 7169, 2023 11 07.
Article
in En
| MEDLINE
| ID: mdl-37935692
ABSTRACT
The precise modification or functionalization of the protein C-terminus is essential but full of challenges. Herein, a chemical approach to modify the C-terminus is developed by fusing a cysteine protease domain on the C-terminus of the protein of interest, which could achieve the non-enzymatic C-terminal functionalization by InsP6-triggered cysteine protease domain self-cleavage. This method demonstrates a highly efficient way to achieve protein C-terminal functionalization and is compatible with a wide range of amine-containing molecules and proteins. Additionally, a reversible C-terminal de-functionalization is found by incubating the C-terminal modified proteins with cysteine protease domain and InsP6, providing a tool for protein functionalization and de-functionalization. Last, various applications of protein C-terminal functionalization are provided in this work, as demonstrated by the site-specific assembly of nanobody drug conjugates, the construction of a bifunctional antibody, the C-terminal fluorescent labeling, and the C-terminal transpeptidation and glycosylation.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Protein C
/
Cysteine Proteases
Language:
En
Journal:
Nat Commun
Journal subject:
BIOLOGIA
/
CIENCIA
Year:
2023
Document type:
Article
Affiliation country:
China