title: 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.
authors.affiliation: Department of Chemistry, University College London , 20 Gordon Street, London, WC1H OAJ, United Kingdom.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Hull
authors.forename: Maria
authors.initials: M
authors.lastname: Livanos
authors.forename: Enrique
authors.initials: E
authors.lastname: Miranda
authors.forename: Mark E B
authors.initials: ME
authors.lastname: Smith
authors.forename: Kerry A
authors.initials: KA
authors.lastname: Chester
authors.forename: James R
authors.initials: JR
authors.lastname: Baker
mesh_terms: D000918:Antibody Specificity; D004220:Disulfides / Q000737:chemistry*; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D057127:Single-Chain Antibodies / Q000737:chemistry* / Q000276:immunology*; D013379:Substrate Specificity
chemical_list: D004220:Disulfides; D057127:Single-Chain Antibodies