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A Plug-and-Play Approach for the De Novo Generation of Dually Functionalized Bispecifics

Maruani, A; Szijj, P; Bahou, C; Nogueira, J; Caddick, S; Baker, JR; Chudasama, V; (2020) A Plug-and-Play Approach for the De Novo Generation of Dually Functionalized Bispecifics. Bioconjugate Chemistry , 31 (3) pp. 520-529. 10.1021/acs.bioconjchem.0c00002. Green open access

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Abstract

Diseases are multifactorial, with redundancies and synergies between various pathways. However, most of the antibody-based therapeutics on the market interact with only one target, thus limiting their efficacy. The targeting of multiple epitopes could improve the therapeutic index of treatment and counteract mechanisms of resistance. To this effect, a new class of therapeutics has emerged: bispecific antibodies. Bispecific formation using chemical methods is rare and low-yielding and/or requires a large excess of one of the two proteins to avoid homodimerization and heterogeneity. In order for chemically prepared bispecifics to deliver their full potential, high-yielding, modular, and reliable cross-linking technologies are required. Herein, we describe a novel approach not only for the rapid and high-yielding chemical generation of bispecific antibodies from native antibody fragments, but also for the site-specific dual functionalization of the resulting bioconjugates. Based on orthogonal clickable functional groups, this strategy enables the assembly of functionalized bispecifics with controlled loading in a modular and convergent manner.

Type: Article
Title: A Plug-and-Play Approach for the De Novo Generation of Dually Functionalized Bispecifics
Open access status: An open access version is available from UCL Discovery
DOI: 10.1021/acs.bioconjchem.0c00002
Publisher version: https://doi.org/10.1021/acs.bioconjchem.0c00002
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Functionalization, Immunology, Hydrocarbons, Peptides and proteins, Biopolymers
UCL classification: UCL
UCL > Provost and Vice Provost Offices > UCL BEAMS
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/10092722
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