Arginine-selective bioconjugation with 4-azidophenyl glyoxal: application to the single and dual functionalisation of native antibodies
| Autor: | Igor Dovgan, Christian D. Muller, Alain Wagner, Sylvain Ursuegui, Steve Hessmann, Chloé Michel, Stéphane Erb, Guilhem Chaubet, Sarah Cianférani |
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| Přispěvatelé: | Conception et application de molécules bioactives (CAMB), Université de Strasbourg (UNISTRA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut Pluridisciplinaire Hubert Curien (IPHC), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Syndivia SAS, Cooltech Applications, Cooltech |
| Rok vydání: | 2018 |
| Předmět: |
Azides
Immunoconjugates medicine.drug_class Arginine 010402 general chemistry Monoclonal antibody Phenylglyoxal 01 natural sciences Biochemistry chemistry.chemical_compound medicine [CHIM]Chemical Sciences Physical and Theoretical Chemistry Guanidine Bioconjugation Cycloaddition Reaction 010405 organic chemistry Lysine Organic Chemistry Antibodies Monoclonal Trastuzumab Combinatorial chemistry Cycloaddition 3. Good health 0104 chemical sciences chemistry Alkynes Reagent Glyoxal Azide Conjugate |
| Zdroj: | Organic and Biomolecular Chemistry Organic and Biomolecular Chemistry, Royal Society of Chemistry, 2018, 16 (8), pp.1305-1311. ⟨10.1039/c7ob02844j⟩ |
| ISSN: | 1477-0539 1477-0520 |
| Popis: | International audience; Here, we introduce 4-azidophenyl glyoxal (APG) as an efficient plug-and-play reagent for the selective functionalisation of arginine residues in native antibodies. The selective reaction between APG and arginines’ guanidine groups allowed a facile introduction of azide groups on the monoclonal antibody trastuzumab (plug stage). These pre-functionalised antibody–azide conjugates were then derivatised during the “play stage” via a biorthogonal cycloaddition reaction with different strained alkynes. This afforded antibody-fluorophore and antibody–oligonucleotide conjugates, all showing preserved antigen selectivity and high stability in human plasma. Due to a lower content of arginines compared to lysines in native antibodies, this approach is thus attractive for the preparation of more homogeneous conjugates. This method proved to be orthogonal to classical lysine-based conjugation and allowed straightforward generation of dual-payload antibody. |
| Databáze: | OpenAIRE |
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