Bispecific Antibody Generated with Sortase and Click Chemistry Has Broad Antiinfluenza Virus Activity

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2014 Nov 12

PMID 25385586

Citations 38

Authors

Koen Wagner

Mark J Kwakkenbos

Yvonne B Claassen

Kelly Maijoor

Martino Bohne

Koenraad F van der Sluijs

Martin D Witte

Diana J van Zoelen

Lisette A Cornelissen

Tim Beaumont

Arjen Q Bakker

Hidde L Ploegh

Hergen Spits

Affiliations

Soon will be listed here.

Abstract

Bispecific antibodies have therapeutic potential by expanding the functions of conventional antibodies. Many different formats of bispecific antibodies have meanwhile been developed. Most are genetic modifications of the antibody backbone to facilitate incorporation of two different variable domains into a single molecule. Here, we present a bispecific format where we have fused two full-sized IgG antibodies via their C termini using sortase transpeptidation and click chemistry to create a covalently linked IgG antibody heterodimer. By linking two potent anti-influenza A antibodies together, we have generated a full antibody dimer with bispecific activity that retains the activity and stability of the two fusion partners.

Citing Articles

Click Chemistry: an overview and recent updates in the medicinal attributes of click-derived heterocycles.

Bishnoi P, Saroha B, Kumar S, Kumar G, Bhardwaj A, Kumari M Mol Divers. 2025; .

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The molecular features of non-peptidic nucleophilic substrates and acceptor proteins determine the efficiency of sortagging.

Bondarchuk T, Zhuravel E, Shyshlyk O, Debelyy M, Pokholenko O, Vaskiv D RSC Chem Biol. 2025; 6(2):295-306.

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Optimized Production of Fc Fusion Proteins by Sortase Enzymatic Ligation.

Apley K, Laflin A, Johnson S, Batrash N, Griffin J, Berkland C Ind Eng Chem Res. 2024; 60(47):16839-16853.

PMID: 38646185 PMC: 11031256. DOI: 10.1021/acs.iecr.1c02842.

Design and engineering of bispecific antibodies: insights and practical considerations.

Madsen A, Pedersen L, Kristensen P, Goletz S Front Bioeng Biotechnol. 2024; 12:1352014.

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An armed anti-immunoglobulin light chain nanobody protects mice against influenza A and B infections.

Liu X, Balligand T, Carpenet C, Ploegh H Sci Immunol. 2023; 8(84):eadg9459.

PMID: 37352373 PMC: 10357953. DOI: 10.1126/sciimmunol.adg9459.

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