In Situ Cyclization of Proteins (INCYPRO): Cross-Link Derivatization Modulates Protein Stability.
J Org Chem
; 85(3): 1476-1483, 2020 02 07.
Article
in En
| MEDLINE
| ID: mdl-31790232
ABSTRACT
Protein macrocyclization represents a very efficient strategy to increase the stability of protein tertiary structures. Here, we describe a panel of novel C3-symmetric tris-electrophilic agents and their use for the cyclization of proteins. These electrophiles are reacted with a protein domain harboring three solvent-exposed cysteine residues, resulting in the in situ cyclization of the protein (INCYPRO). We observe a clear dependency of cross-linking rates on the electrophilicity. All nine obtained cross-linked protein versions show considerably increased thermal stability (up to 29 °C increased melting temperature) when compared to that of the linear precursor. Most interestingly, the degree of stabilization correlates with the hydrophilicity of the cross-link. These results will support the development of novel cross-linked proteins and enable a more rational design process.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Proteins
Language:
En
Journal:
J Org Chem
Year:
2020
Type:
Article
Affiliation country:
Netherlands