Introducing Glycolinkers for the Functionalization of Cytotoxic Drugs and Applications in Antibody–Drug Conjugation Chemistry |
| |
| Authors: | Dr. Filip S. Ekholm Henna Pynnönen Anja Vilkman Virve Pitkänen Dr. Jari Helin Juhani Saarinen Tero Satomaa |
| |
| Affiliation: | 1. Glykos Finland Ltd., Helsinki, Finland;2. Department of Chemistry, University of Helsinki, Helsinki, Finland |
| |
| Abstract: | 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. |
| |
| Keywords: | antibody– drug conjugates bioconjugation carbohydrates cytotoxic activity structural characterization |
|
|
