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Development of a dual-functional conjugate of antigenic peptide and Fc-III mimetics (DCAF) for targeted antibody blocking

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Abstract

Targeted antibody blocking enables characterization of binding sites on immunoglobulin G (IgG), and can efficiently eliminate harmful antibodies from organisms. In this report, we present a novel peptide—denoted as a dual-functional conjugate of antigenic peptide and Fc-III mimetics (DCAF)—for targeted blocking of antibodies. Synthesis of DCAF was achieved by native chemical ligation, and the molecule consists of three functional parts: a specific antigenic peptide, a linker and the Fc-III mimetic peptide, which has a high affinity toward the Fc region of IgG molecules. We demonstrate that DCAF binds the cognate antibody with high selectivity by simultaneously binding to the Fab and Fc regions of IgG. Animal experiments revealed that DCAF molecules diminish the antibody-dependent enhancement effect in a dengue virus infection model, and rescue the acetylcholine receptor by inhibiting the complement cascade in a myasthenia gravis model. These results suggest that DCAFs could have utility in the development of new therapeutics against harmful antibodies.

Graphical abstract: Development of a dual-functional conjugate of antigenic peptide and Fc-III mimetics (DCAF) for targeted antibody blocking

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Publication details

The article was received on 27 Nov 2018, accepted on 28 Jan 2019 and first published on 28 Jan 2019


Article type: Edge Article
DOI: 10.1039/C8SC05273E
Citation: Chem. Sci., 2019, Advance Article
  • Open access: Creative Commons BY license
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    Development of a dual-functional conjugate of antigenic peptide and Fc-III mimetics (DCAF) for targeted antibody blocking

    L. Zhang, H. Shen, Y. Gong, X. Pang, M. Yi, L. Guo, J. Li, S. Arroyo, X. Lu, S. Ovchinnikov, G. Cheng, X. Liu, X. Jiang, S. Feng and H. Deng, Chem. Sci., 2019, Advance Article , DOI: 10.1039/C8SC05273E

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