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Maria Raposo, New University of Lisbon, Portugal Updates Copyright 2022 Han, Wang, Wang, Lang, Xia, Jia and Chen

A key challenge stems from the structural complexity of conjugating a large antibody (~150 kDa) with a multifunctional PROTAC, often generating heterogeneous species that are difficult to optimize

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The propeptide of the VDP binds to the lumenal domain of GGCX, which stabilizes transmembrane helices 6 and 7 of GGCX to create the VK-binding pocket