Forte, N;
Livanos, M;
Miranda, E;
Morais, M;
Yang, X;
Rajkumar, VS;
Chester, KA;
... Baker, JR; + view all
(2018)
Tuning the Hydrolytic Stability of Next Generation Maleimide Cross-Linkers Enables Access to Albumin-Antibody Fragment Conjugates and tri-scFvs.
Bioconjugate Chemistry
, 29
(2)
pp. 486-492.
10.1021/acs.bioconjchem.7b00795.
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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.
| Type: | Article |
|---|---|
| Title: | Tuning the Hydrolytic Stability of Next Generation Maleimide Cross-Linkers Enables Access to Albumin-Antibody Fragment Conjugates and tri-scFvs |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1021/acs.bioconjchem.7b00795 |
| Publisher version: | http://dx.doi.org/10.1021/acs.bioconjchem.7b00795 |
| Language: | English |
| Additional information: | ACS AuthorChoice - This is an open access article published under a Creative Commons Attribution (CC-BY) License, which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited. |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Physical Sciences, Biochemical Research Methods, Biochemistry & Molecular Biology, Chemistry, Multidisciplinary, Chemistry, Organic, Chemistry, UNNATURAL AMINO-ACIDS, HALF-LIFE EXTENSION, BISPECIFIC ANTIBODIES, DRUG CONJUGATE, FUSION PROTEINS, CANCER-THERAPY, THERAPEUTICS, PLATFORM, CYSTEINE, POTENT |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Oncology UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Biochemical Engineering UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > Dept of Chemistry |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10048306 |
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