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Papers Published

1. Bellucci, JJ; Bhattacharyya, J; Chilkoti, A, A noncanonical function of sortase enables site-specific conjugation of small molecules to lysine residues in proteins., Angewandte Chemie (International ed. in English), vol. 54 no. 2 (January, 2015), pp. 441-445 [doi] .
   (last updated on 2026/01/18)

   Abstract:
   We provide the first demonstration that isopeptide ligation, a noncanonical activity of the enzyme sortase A, can be used to modify recombinant proteins. This reaction was used in vitro 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 ε-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 sortase A. 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.