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Encoding latent SuFEx reactive meta-fluorosulfate tyrosine to expand covalent bonding of proteins.

ABSTRACT: The introduction of new covalent bonds into proteins is affording novel avenues for protein research and applications, yet it remains difficult to generate covalent linkages at all possible sites and across diverse protein classes. Herein, we genetically encoded meta-fluorosulfate-L-tyrosine (mFSY) to selectively react with lysine, tyrosine, and histidine via proximity-enabled SuFEx reaction. mFSY was able to target residues that were elusive for previous unnatural amino acids, and permitted engineering of various proteins including affibody, nanobody, and Fab into covalent binders that irreversibly cross-linked EGFR and HER2. mFSY is thus valuable for developing covalent proteins for biological research, synthetic biology, and biotherapeutics.

SUBMITTER: Klauser PC

PROVIDER: S-EPMC9816398 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Encoding latent SuFEx reactive meta-fluorosulfate tyrosine to expand covalent bonding of proteins.

Klauser Paul C PC Berdan Viktoriya Y VY Cao Li L Wang Lei L

Chemical communications (Cambridge, England) 20220614 48

The introduction of new covalent bonds into proteins is affording novel avenues for protein research and applications, yet it remains difficult to generate covalent linkages at all possible sites and across diverse protein classes. Herein, we genetically encoded <i>meta</i>-fluorosulfate-L-tyrosine (mFSY) to selectively react with lysine, tyrosine, and histidine <i>via</i> proximity-enabled SuFEx reaction. mFSY was able to target residues that were elusive for previous unnatural amino acids, and ...[more]

PMID: 35621237

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