Multifunctional Glycoconjugates for Recruiting Natural Antibodies against Cancer Cells

Autor: David Goyard, Biagio Todaro, Nathalie Berthet, Eugénie Laigre, Didier Boturyn, Claire Tiertant, Olivier Renaudet, Benjamin Liet
Přispěvatelé: Département de Chimie Moléculaire - Ingéniérie et Intéractions BioMoléculaires (DCM - I2BM), Département de Chimie Moléculaire (DCM), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Université Joseph Fourier - Grenoble 1 (UJF)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Liet, B., Laigre, E., Goyard, D., Todaro, B., Tiertant, C., Boturyn, D., Berthet, N., Renaudet, O.
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Glycoconjugate
Integrin
Ligands
010402 general chemistry
Rhamnose
01 natural sciences
Antibodies
Catalysis
Flow cytometry
Immune system
In vivo
Settore BIO/10 - Biochimica
Cell Line
Tumor
medicine
cancer
Humans
[CHIM]Chemical Sciences
Cytotoxic T cell
[SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Biochemistry [q-bio.BM]
chemistry.chemical_classification
Full Paper
medicine.diagnostic_test
biology
010405 organic chemistry
[CHIM.ORGA]Chemical Sciences/Organic chemistry
Organic Chemistry
Settore CHIM/06 - Chimica Organica
General Chemistry
Full Papers
multivalency
Flow Cytometry
Integrin alphaVbeta3
Molecular biology
glycoconjugates
3. Good health
0104 chemical sciences
chemistry
Antibody Recruitment | Hot Paper
click chemistry
Cancer cell
biology.protein
Immunization
Antibody
Zdroj: Chemistry-A European Journal
Chemistry-A European Journal, Wiley-VCH Verlag, 2019, ⟨10.1002/chem.201903327⟩
Chemistry-A European Journal, Wiley-VCH Verlag, 2019, 25, pp.15508-15515. ⟨10.1002/chem.201903327⟩
Chemistry (Weinheim an Der Bergstrasse, Germany)
Chemistry – A European Journal
ISSN: 0947-6539
1521-3765
Popis: We have developed a fully synthetic and multifunctional antibody‐recruiting molecule (ARM) to guide natural antibodies already present in the blood stream against cancer cells without pre‐immunization. Our ARM is composed of antibody and tumor binding modules (i.e., ABM and TBM) displaying clustered rhamnose and cyclo‐RGD, respectively. By using a stepwise approach, we have first demonstrated the importance of multivalency for efficient recognition with naturel IgM and αvβ3 integrin expressing M21 tumor cell line. Once covalently conjugated by click chemistry, we confirmed by flow cytometry and confocal microscopy that the recognition properties of both the ABM and TBM are conserved, and more importantly, that the resulting ARM promotes the formation of a ternary complex between natural IgM and cancer cells, which is required for the stimulation of the cytotoxic immune response in vivo. Due to the efficiency of the synthetic process, a larger diversity of heterovalent ligands could be easily explored by using the same multivalent approach and could open new perspectives in this field.
Synthetic commander: A potent synthetic and multifunctional antibody‐recruiting molecule is synthesized through the combination of antibody and tumor binding modules, thereby providing a candidate that promotes the formation of a ternary complex between natural antibodies and cancer cells, which is required for the stimulation of the cytotoxic immune response in vivo.
Databáze: OpenAIRE
Externí odkaz: