Ethynylphosphonamidates for the Rapid and Cysteine‐Selective Generation of Efficacious Antibody–Drug Conjugates

Abstract: Requirements for novel bioconjugation reactions for the synthesis of antibody–drug conjugates (ADCs) are exceptionally high, since conjugation selectivity as well as the stability and hydrophobicity of linkers and payloads drastically influence the performance and safety profile of the final product. We report Cys‐selective ethynylphosphonamidates as new reagents for the rapid generation of efficacious ADCs from native non‐engineered monoclonal antibodies through a simple one‐pot reduction and alkylation. Ethynylphosphonamidates can be easily substituted with hydrophilic residues, giving rise to electrophilic labeling reagents with tunable solubility properties. We demonstrate that ethynylphosphonamidate‐linked ADCs have excellent properties for next‐generation antibody therapeutics in terms of serum stability and in vivo antitumor activity.

Object Details

• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch

References and Relationships

• Bibliographic citation: Ethynylphosphonamidates for the Rapid and Cysteine‐Selective Generation of Efficacious Antibody–Drug Conjugates ; volume:58 ; number:34 ; year:2019 ; pages:11631-11636 ; extent:6 ; Angewandte Chemie / International edition. International edition ; 58, Heft 34 (2019), 11631-11636 (gesamt 6)

Contributors, Places and Time

• Creator: Kasper, Marc‐André ; Stengl, Andreas ; Ochtrop, Philipp ; Gerlach, Marcus ; Stoschek, Tina ; Schumacher, Dominik ; Helma, Jonas ; Penkert, Martin ; Krause, Eberhard ; Leonhardt, Heinrich ; Hackenberger, Christian

Further information

• DOI: 10.1002/anie.201904193
• URN: urn:nbn:de:101:1-2022081108362669252747
• Rights: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Last update: 15.08.2025, 7:29 AM CEST