Open AccessHomogeneous Bispecifics by Disulfide Bridging
Author(s) -
Elizabeth Hull,
Maria Livanos,
Enrique Miranda,
Mark E. Smith,
Kerry Chester,
James R. Baker
Publication year - 2014
Publication title -
bioconjugate chemistry
Language(s) - Uncategorized
Resource type - Journals
SCImago Journal Rank - 1.279
H-Index - 172
eISSN - 1520-4812
pISSN - 1043-1802
DOI - 10.1021/bc5002467
Subject(s) - chemistry , disulfide bond , linker , homogeneous , bridging (networking) , antibody , combinatorial chemistry , in vitro , stereochemistry , conjugate , biochemistry , immunology , computer network , mathematical analysis , physics , mathematics , biology , computer science , thermodynamics , operating system
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.