Bis‐ethynylphosphonamidates as an Modular Conjugation Platform to Generate Multi‐Functional Protein‐ and Antibody‐Drug‐Conjugates

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Abstract: Bis‐ethynylphosphonamidates allow for a simple chemoselective addition of two thiol‐containing modules in a row. We describe four such bis‐electrophiles that carry different functional O‐substituents with tunable hydrophilicity and enable further subsequent conjugations, thus facilitating a simple protocol for constructing protein‐protein conjugates. An increased spacer length between the two ethynylphosphonamidates simplifies the formation of a conjugate from two bulky proteins. We apply these reagents to obtain homogeneous Antibody‐Drug‐Conjugates (ADCs) from DM1 and trastuzumab with excellent cytotoxicity and selectivity for the targeted cell line. Moreover, a bis‐ethynylphosphonamidate, carrying an additional alkyne for a chemoselective triple conjugation, has been subjected to fluorescent labeling of an ADC specifically at the drug site give an Antibody‐Drug‐Fluorophore‐Conjugate (ADFC), allowing for the observation of intracellular trafficking after ADC uptake into the targeted cell.

Location: Deutsche Nationalbibliothek Frankfurt am Main

Extent: Online-Ressource

Language: Englisch

Bibliographic citation: Bis‐ethynylphosphonamidates as an Modular Conjugation Platform to Generate Multi‐Functional Protein‐ and Antibody‐Drug‐Conjugates ; day:18 ; month:01 ; year:2022 ; extent:1
European journal of organic chemistry ; (18.01.2022) (gesamt 1)

Creator: Kasper, Marc‐André
Lassak, Lukas
Vogl, Annette M.
Mai, Isabelle
Helma, Jonas
Schumacher, Dominik
Hackenberger, Christian

DOI: 10.1002/ejoc.202101389

URN: urn:nbn:de:101:1-2022011814204191571221

Rights: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.

Last update: 15.08.2025, 7:31 AM CEST

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Kasper, Marc‐André
Lassak, Lukas
Vogl, Annette M.
Mai, Isabelle
Helma, Jonas
Schumacher, Dominik
Hackenberger, Christian

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