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US 2026/0200969 A1Published application
Methods for Synthesis of Protein Hetero-polymers
AssigneeThe Regents of the University of California
InventorsAlanna Schepartz Shrader, Leah Tang Roe
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Abstract
A method for synthesis of protein hetero-polymers uses an intramolecular Backbone Extension Acyl Rearrangement (BEAR) reactions to orthogonally and site-specifically embed a β-, γ- or δ-amino acid residue into proteins.
Claims20
A method of protein backbone editing, the method comprising:
- a) providing a cell engineered to express an orthogonal aminoacyl-tRNA synthetase under conditions wherein the synthetase accepts an α-hydroxy acid or α-thiol acid monomer comprising a side chain bearing a masked nucleophile, and the monomer is incorporated into a protein translated in the cell,
- b) post-translationally unmasking the nucleophile of the incorporated monomer, wherein the unmasked monomer engages in a thermodynamically favored intramolecular Backbone Extension Acyl Rearrangement (BEAR) reaction that edits the protein backbone.
A method of protein backbone editing, the method comprising:
- using a proximity-guided intramolecular rearrangement that edits the protein backbone post-translationally, wherein an orthogonal aminoacyl-tRNA synthetase enzyme accepts diverse monomers, including those whose side chains contain masked nucleophiles,
- wherein a monomer whose side chains contains a masked nucleophile is introduced into the protein translated in vivo, followed by nucleophile unmasking, to provide a thermodynamically favored intramolecular Backbone Extension Acyl Rearrangement (BEAR) reaction that edits the protein backbone to install an extended backbone monomer.
Dependencies are inferred from the claim text.