- Site-Specific Tandem Knoevenagel Condensation-Michael Addition to Generate Antibody-Drug Conjugates
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Expanded ligation techniques are sorely needed to generate unique linkages for the growing field of functionally enhanced proteins. To address this need, we present a unique chemical ligation that involves the double addition of a pyrazolone moiety with an aldehyde-labeled protein. This ligation occurs via a tandem Knoevenagel condensation-Michael addition. A pyrazolone reacts with an aldehyde to generate an enone, which undergoes subsequent attack by a second pyrazolone to generate a bis-pyrazolone species. This rapid and facile ligation technique is performed under mild conditions in the absence of catalyst to generate new architectures that were previously inaccessible via conventional ligation reactions. Using this unique ligation, we generated three site-specifically labeled antibody-drug conjugates (ADCs) with an average of four drugs to one antibody. The in vitro and in vivo efficacies along with pharmacokinetic data of the site-specific ADCs are reported.
- Kudirka, Romas A.,Barfield, Robyn M.,McFarland, Jesse M.,Drake, Penelope M.,Carlson, Adam,Banas, Stefanie,Zmolek, Wes,Garofalo, Albert W.,Rabuka, David
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- Pyrazolone-based glycoprotein-bound membrane dye as well as preparation method and application thereof
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The invention discloses a pyrazolone-based glycoprotein-bound membrane dye. The general formula structure of the membrane dye is as shown in formula (I), and in the formula (I), R1 is a fluorescent chromophore dye structure with an O terminal or an N terminal; R2 is at least one selected from -O-, -O-O-, -S-, -NH-, -NHNH- or -ONH-; and R3 is at least one selected from the shown groups. The invention relates to a biosensor for long-retention cell membrane tracking imaging, and/or for rapid and accurate imaging of cell membranes at low concentrations, and/or for observing cell division and migration processes, and/or for membrane labeling to distinguish co-cultured cells, and/or for distinguishing fluorescence signals of different cells, and/or for labeling and grouping of cells, and/or for tracking of passage cells.
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Paragraph 0067; 0075-0078
(2021/08/07)
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- Thrombopoietin mimetics
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Invented are non-peptide TPO mimetics. Also invented is a method of treating thrombocytopenia, in a mammal, including a human, in need thereof which comprises administering to such mammal an effective amount of a selected azo-pyrazole derivative.
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