Introducing Glycolinkers for the Functionalization of Cytotoxic Drugs and Applications in Antibody-Drug Conjugation Chemistry
| Autor: | Juhani Saarinen, Filip S. Ekholm, Anja Vilkman, Tero Satomaa, Virve Pitkänen, Henna Pynnönen, Jari Helin |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Immunoconjugates Cell Survival Molecular Conformation Antineoplastic Agents Biochemistry 03 medical and health sciences chemistry.chemical_compound Structure-Activity Relationship Cell Line Tumor Drug Discovery Humans General Pharmacology Toxicology and Pharmaceutics Derivatization Cytotoxicity Bifunctional Cell Proliferation Pharmacology Bioconjugation biology Dose-Response Relationship Drug Organic Chemistry Antibodies Monoclonal 3. Good health body regions 030104 developmental biology chemistry biology.protein Molecular Medicine Surface modification Antibody Linker Oligopeptides Conjugate |
| Zdroj: | ChemMedChem. 11(22) |
| ISSN: | 1860-7187 |
| Popis: | Antibody–drug conjugates (ADCs) are promising alternatives to naked antibodies for selective drug-delivery applications and treatment of diseases such as cancer. Construction of ADCs relies upon site-selective, efficient and mild conjugation technologies. The choice of a chemical linker is especially important, as it affects the overall properties of the ADC. We envisioned that hydrophilic bifunctional chemical linkers based on carbohydrates would be a useful class of derivatization agents for the construction of linker–drug conjugates and ADCs. Herein we describe the synthesis of carbohydrate-based derivatization agents, glycolinker–drug conjugates featuring the tubulin inhibitor monomethyl auristatin E and an ADC based on an anti-EGFR antibody. In addition, an initial in vitro cytotoxicity evaluation of the individual components and the ADC is provided against EGFR-positive cancer cells. |
| Databáze: | OpenAIRE |
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