Bis‐ethynylphosphonamidates as an Modular Conjugation Platform to Generate Multi‐Functional Protein‐ and Antibody‐Drug‐Conjugates
dc.contributor.author | Kasper, Marc-André | |
dc.contributor.author | Lassak, Lukas | |
dc.contributor.author | Vogl, Annette | |
dc.contributor.author | Mai, Isabelle | |
dc.contributor.author | Helma, Jonas | |
dc.contributor.author | Schumacher, Dominik | |
dc.contributor.author | Hackenberger, Christian | |
dc.date.accessioned | 2022-06-23T11:24:29Z | |
dc.date.available | 2022-06-23T11:24:29Z | |
dc.date.issued | 2022-01-18 | none |
dc.date.updated | 2022-06-14T23:52:35Z | |
dc.identifier.uri | http://edoc.hu-berlin.de/18452/25489 | |
dc.description.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. | eng |
dc.description.sponsorship | LMU center | |
dc.description.sponsorship | Deutsche Forschungsgemeinschaft (DFG) | |
dc.description.sponsorship | Einstein Foundation Berlin http://dx.doi.org/10.13039/501100006188 | |
dc.description.sponsorship | Boehringer-Ingelheim Foundation | |
dc.description.sponsorship | Fonds der Chemischen Industrie | |
dc.description.sponsorship | Leibniz Association http://dx.doi.org/10.13039/501100001664 | |
dc.description.sponsorship | German Federal Ministry for Economic Affairs and Energy | |
dc.description.sponsorship | European Social Fund http://dx.doi.org/10.13039/501100004895 | |
dc.description.sponsorship | Bavarian Ministry of Economic Affairs, Regional Development and Energy http://dx.doi.org/10.13039/501100020639 | |
dc.language.iso | eng | none |
dc.publisher | Humboldt-Universität zu Berlin | |
dc.rights | (CC BY-NC-ND 4.0) Attribution-NonCommercial-NoDerivatives 4.0 International | ger |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/4.0/ | |
dc.subject | Alkynes | eng |
dc.subject | Antibodies | eng |
dc.subject | Conjugation | eng |
dc.subject | Drug delivery | eng |
dc.subject | Protein modifications | eng |
dc.subject.ddc | 540 Chemie und zugeordnete Wissenschaften | none |
dc.title | Bis‐ethynylphosphonamidates as an Modular Conjugation Platform to Generate Multi‐Functional Protein‐ and Antibody‐Drug‐Conjugates | none |
dc.type | article | |
dc.identifier.urn | urn:nbn:de:kobv:11-110-18452/25489-1 | |
dc.identifier.doi | http://dx.doi.org/10.18452/24824 | |
dc.type.version | publishedVersion | none |
local.edoc.pages | 9 | none |
local.edoc.type-name | Zeitschriftenartikel | |
local.edoc.container-type | periodical | |
local.edoc.container-type-name | Zeitschrift | |
dc.description.version | Peer Reviewed | none |
dc.identifier.eissn | 1099-0690 | |
dcterms.bibliographicCitation.doi | 10.1002/ejoc.202101389 | none |
dcterms.bibliographicCitation.journaltitle | European journal of organic chemistry | none |
dcterms.bibliographicCitation.volume | 2022 | none |
dcterms.bibliographicCitation.issue | 10 | none |
dcterms.bibliographicCitation.articlenumber | e202101389 | none |
dcterms.bibliographicCitation.originalpublishername | Wiley-VCH Verl. | none |
dcterms.bibliographicCitation.originalpublisherplace | Weinheim | none |
bua.department | Mathematisch-Naturwissenschaftliche Fakultät | none |