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Expanding the Scope of Antibody Rebridging with New Pyridazinedione-TCO Constructs.

ABSTRACT: Disulfide rebridging methods have recently emerged as a route to hinge region-specific antibody modification, and there exist numerous examples of successful rebridging chemistry applied to clinically relevant human IgG1 antibodies. Here, dibromopyridazinedione disulfide rebridging is adapted to fast trans-cyclooctene/tetrazine (TCO/Tz) bioorthogonal ligations and extended beyond therapeutic human IgG1 antibodies for the first time to include mouse and rat monoclonal antibodies integral to multiplexed analytical diagnostics. In spite of a common architecture, only a subset of antibody host species and IgG isotype subclasses can be rebridged, highlighting the intricate relationship between hinge region sequence, structure, biological activity, and the conjugation chemistry of IgG antibodies.

SUBMITTER: Marquard AN

PROVIDER: S-EPMC7788567 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Expanding the Scope of Antibody Rebridging with New Pyridazinedione-TCO Constructs.

Marquard Angela N AN Carlson Jonathan C T JCT Weissleder Ralph R

Bioconjugate chemistry 20200428 6

Disulfide rebridging methods have recently emerged as a route to hinge region-specific antibody modification, and there exist numerous examples of successful rebridging chemistry applied to clinically relevant human IgG1 antibodies. Here, dibromopyridazinedione disulfide rebridging is adapted to fast trans-cyclooctene/tetrazine (TCO/Tz) bioorthogonal ligations and extended beyond therapeutic human IgG1 antibodies for the first time to include mouse and rat monoclonal antibodies integral to multi ...[more]

PMID: 32286045

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