In Situ Cyclization of Proteins (INCYPRO): Cross-Link Derivatization Modulates Protein Stability.
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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.
SUBMITTER: Neubacher S
PROVIDER: S-EPMC7011175 | biostudies-literature | 2020 Feb
REPOSITORIES: biostudies-literature
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