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2022-01-18Zeitschriftenartikel DOI: 10.1002/ejoc.202101389
Bis‐ethynylphosphonamidates as an Modular Conjugation Platform to Generate Multi‐Functional Protein‐ and Antibody‐Drug‐Conjugates
dc.contributor.authorKasper, Marc-André
dc.contributor.authorLassak, Lukas
dc.contributor.authorVogl, Annette
dc.contributor.authorMai, Isabelle
dc.contributor.authorHelma, Jonas
dc.contributor.authorSchumacher, Dominik
dc.contributor.authorHackenberger, Christian
dc.date.accessioned2022-06-23T11:24:29Z
dc.date.available2022-06-23T11:24:29Z
dc.date.issued2022-01-18none
dc.date.updated2022-06-14T23:52:35Z
dc.identifier.urihttp://edoc.hu-berlin.de/18452/25489
dc.description.abstractBis-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.sponsorshipLMU center
dc.description.sponsorshipDeutsche Forschungsgemeinschaft (DFG)
dc.description.sponsorshipEinstein Foundation Berlin http://dx.doi.org/10.13039/501100006188
dc.description.sponsorshipBoehringer-Ingelheim Foundation
dc.description.sponsorshipFonds der Chemischen Industrie
dc.description.sponsorshipLeibniz Association http://dx.doi.org/10.13039/501100001664
dc.description.sponsorshipGerman Federal Ministry for Economic Affairs and Energy
dc.description.sponsorshipEuropean Social Fund http://dx.doi.org/10.13039/501100004895
dc.description.sponsorshipBavarian Ministry of Economic Affairs, Regional Development and Energy http://dx.doi.org/10.13039/501100020639
dc.language.isoengnone
dc.publisherHumboldt-Universität zu Berlin
dc.rights(CC BY-NC-ND 4.0) Attribution-NonCommercial-NoDerivatives 4.0 Internationalger
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectAlkyneseng
dc.subjectAntibodieseng
dc.subjectConjugationeng
dc.subjectDrug deliveryeng
dc.subjectProtein modificationseng
dc.subject.ddc540 Chemie und zugeordnete Wissenschaftennone
dc.titleBis‐ethynylphosphonamidates as an Modular Conjugation Platform to Generate Multi‐Functional Protein‐ and Antibody‐Drug‐Conjugatesnone
dc.typearticle
dc.identifier.urnurn:nbn:de:kobv:11-110-18452/25489-1
dc.identifier.doi10.1002/ejoc.202101389none
dc.identifier.doihttp://dx.doi.org/10.18452/24824
dc.type.versionpublishedVersionnone
local.edoc.container-titleEuropean journal of organic chemistrynone
local.edoc.pages9none
local.edoc.type-nameZeitschriftenartikel
local.edoc.institutionMathematisch-Naturwissenschaftliche Fakultätnone
local.edoc.container-typeperiodical
local.edoc.container-type-nameZeitschrift
local.edoc.container-publisher-nameWiley-VCH Verl.none
local.edoc.container-publisher-placeWeinheimnone
local.edoc.container-volume2022none
local.edoc.container-issue10none
dc.description.versionPeer Reviewednone
local.edoc.container-articlenumbere202101389none
dc.identifier.eissn1099-0690

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