Orthogonal cross-linked proteins, methods for their preparation and uses

Abstract

Compounds, proteins, crosslinked proteins, compositions thereof, and methods for their manufacture and use. The compounds may be α-amino acids, and include one or more β-lactam groups, one or more triazole groups, substituted analogs thereof, or any combination thereof. The proteins include one or more amino acid residues, each of which includes a β-lactam group, a triazole group, or substituted analogs thereof. The proteins can be produced by recombinant methods using one or more compounds. The crosslinked proteins include one or more intramolecular crosslinks and / or one or more intermolecular crosslinks. In various examples, the crosslinks are formed, for example, in solution or in vivo, by a β-lactam ring-opening reaction or an acyl transfer reaction due to the proximity between a β-lactam group or a triazole group and a nucleophilic side chain group, where both groups are present on a single polypeptide or on different polypeptide chains. The crosslinked proteins can be used in therapeutic methods.

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