A Noncanonical Function Of Sortase Enables Site-Specific Conjugation Of Small Molecules To Lysine Residues In Proteins
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION(2015)
摘要
We provide the first demonstration that isopeptide ligation, a noncanonical activity of the enzyme sortaseA, can be used to modify recombinant proteins. This reaction was used invitro to conjugate small molecules to a peptide, an engineered targeting protein, and a full-length monoclonal antibody with an exquisite level of control over the site of conjugation. Attachment to the protein substrate occurred exclusively through isopeptide bonds at a lysine epsilon-amino group within a specific amino acid sequence. This reaction allows more than one molecule to be site-specifically conjugated to a protein at internal sites, thereby overcoming significant limitations of the canonical native peptide ligation reaction catalyzed by sortaseA. Our method provides a unique chemical ligation procedure that is orthogonal to existing methods, supplying a new method to site-specifically modify lysine residues that will be a valuable addition to the protein conjugation toolbox.
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关键词
biotechnology,protein modification,bioconjugation,sortase
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