Mr. Dingdong Yuan


Site-selective acetylation at a single lysine residue in an antibody, reaching the accuracy, precision, and reliability of enzyme-catalyzed lysine acylation reactions, is particularly challenging [1]. Here, we report the acylation of human Immunoglobulin G (IgG) at one single lysine residue on the Fc region of the heavy chain via a peptide-guided, proximity-driven group transfer reaction. The Fc-binding peptide ester acetylated human IgGs, including several therapeutic monoclonal antibodies for immunotherapy, exclusively at Lys 248 of the heavy chain. Using this approach, we synthesized an anti-HER2 immunoliposome for better fusion efficiency to HER2+ cells and an anti-HER2/anti-CD3 bispecific antibody complex (bsAbC), which efficiently cross-linked HER2+ cells and CD3+ cells. The bsAbC showed an in vitro effector-cell-mediated cytotoxicity at nanomolar concentrations. Compared with bispecific antibodies (bsAbs) [2], bsAbCs are constructed based on native IgGs and contain two antigen-binding sites to each antigen, twice that of bsAbs.



  1. Carter, P., & Lazar, G. Nature Reviews Drug Discovery, 2018, 17 197-223.
  2. Paul W. H. I. Parren, et al, Nature Reviews Drug Discovery, 2019, 18, 585.


University: CUHK

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