Format:
1 Online-Ressource (9 Seiten)
Content:
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.
Content:
Peer Reviewed
In:
Weinheim : Wiley-VCH Verl., 2022,10
Language:
English
DOI:
10.1002/ejoc.202101389
URN:
urn:nbn:de:kobv:11-110-18452/25489-1
URL:
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