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Updated: Feb 15, 2026

Bacterial Inner-membrane Display for Screening a Library of Antibody Fragments
Published on: October 15, 2016
Tuning the Hydrolytic Stability of Next Generation Maleimide Cross-Linkers Enables Access to Albumin-Antibody
Nafsika Forte1, Maria Livanos2, Enrique Miranda2
1Department of Chemistry, University College London , 20 Gordon Street, London, WC1H OAJ, United Kingdom.
Abstract:
We describe investigations to expand the scope of next generation maleimide cross-linkers for the construction of homogeneous protein-protein conjugates. Diiodomaleimides are shown to offer the ideal properties of rapid bioconjugation with reduced hydrolysis, allowing the cross-linking of even sterically hindered systems. The optimized linkers are exploited to link human serum albumin to antibody fragments (Fab or scFv) as a prospective half-life extension platform, with retention of antigen binding and robust serum stability. Finally, a triprotein conjugate is formed, by linking scFv antibody fragments targeting carcinoembryonic antigen. This tri-scFv is shown to infer a combination of greater antigen avidity and increased in vivo half-life, representing a promising platform for antibody therapeutic development.
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