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Homogeneous bispecifics by disulfide bridging.

ABSTRACT: We report on a chemical platform to generate site-specific, homogeneous, antibody-antibody conjugates by targeting and bridging disulfide bonds. A bispecific antibody construct was produced in good yield through simple reduction and bridging of antibody fragment disulfide bonds, using a readily synthesized bis-dibromomaleimide cross-linker. Binding activity of antibodies was maintained, and in vitro binding of target antigens was observed. This technology is demonstrated through linking scFv and Fab antibody fragments, showing its potential for the construction of a diverse range of bispecifics.

SUBMITTER: Hull EA

PROVIDER: S-EPMC4458859 | biostudies-other | 2014 Aug

REPOSITORIES: biostudies-other

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Homogeneous bispecifics by disulfide bridging.

Hull Elizabeth A EA Livanos Maria M Miranda Enrique E Smith Mark E B ME Chester Kerry A KA Baker James R JR

Bioconjugate chemistry 20140801 8

We report on a chemical platform to generate site-specific, homogeneous, antibody-antibody conjugates by targeting and bridging disulfide bonds. A bispecific antibody construct was produced in good yield through simple reduction and bridging of antibody fragment disulfide bonds, using a readily synthesized bis-dibromomaleimide cross-linker. Binding activity of antibodies was maintained, and in vitro binding of target antigens was observed. This technology is demonstrated through linking scFv and ...[more]

PMID: 25033024

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