title: Introducing Glycolinkers for the Functionalization of Cytotoxic Drugs and Applications in Antibody-Drug Conjugation Chemistry.
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.
authors: Glykos Finland Ltd., Viikinkaari 6, 00790, Helsinki, Finland.|Department of Chemistry, University of Helsinki, PO Box 55, A. I. Virtasen aukio 1, 00014, Helsinki, Finland.
authors: Filip S
authors: FS
authors: Ekholm
authors: Glykos Finland Ltd., Viikinkaari 6, 00790, Helsinki, Finland.
authors: Henna
authors: H
authors: Pynnönen
authors: Glykos Finland Ltd., Viikinkaari 6, 00790, Helsinki, Finland.
authors: Anja
authors: A
authors: Vilkman
authors: Glykos Finland Ltd., Viikinkaari 6, 00790, Helsinki, Finland.
authors: Virve
authors: V
authors: Pitkänen
authors: Glykos Finland Ltd., Viikinkaari 6, 00790, Helsinki, Finland.
authors: Jari
authors: J
authors: Helin
authors: Glykos Finland Ltd., Viikinkaari 6, 00790, Helsinki, Finland.
authors: Juhani
authors: J
authors: Saarinen
authors: Glykos Finland Ltd., Viikinkaari 6, 00790, Helsinki, Finland.
authors: Tero
authors: 0000-0001-8547-2661
authors: T
authors: Satomaa
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D018796:Immunoconjugates / Q000737:chemistry / Q000494:pharmacology*; D008968:Molecular Conformation; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D018796:Immunoconjugates; D009842:Oligopeptides; C495575:monomethyl auristatin E
keywords: antibody-drug conjugates; bioconjugation; carbohydrates; cytotoxic activity; structural characterization