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. 2020 Apr 27;15(6):1306–1312. doi: 10.1021/acschembio.0c00285

Figure 1.

Figure 1

(A) Proposed mode of action of an antibody–PROTAC conjugate, resulting in HER2-dependent protein degradation. (B) Structures of compounds 1 and 2. (C) Overall structure of Ab-PROTAC 3. (D) LC-MS analysis of trastuzumab-NGM-PROTAC conjugate (Ab-PROTAC 3) and the deconvoluted ion series mass spectrum. Observed mass of 152 010 corresponds to full antibody modified with four NGM-BCN-PROTAC molecules, where all NGM moieties are hydrolyzed to maleamic acids (expected: 152 008); 76 005 corresponds to the isomeric form in which the hinge cysteines are bridged in an intrachain manner (expected: 76 004). (E) Hydrolytic stability of Ab-PROTAC 3 determined by liquid chromatography–mass spectroscopy (LC-MS).