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d Davis, JACS 125 (2022) 9403 What would one like to acplish in total catalyst synthesis? ? Shape of the cavity ? Path to cavity ? Ability to design and position ancillary groups ? Complete atomic control of active site Eliminated pore diffusion control, Little shape selectivity. A. Corma, U. Diaz, . Domine, V. Forn233。s, Angew. Chem. Int. Ed. 39 (2022) 1499. (h00) K. Polborn and K. Severin, Chem. Commun. (1999) 24812482. Molecular Imprinting Cat. 4 made from 2。 control cat. 5 made from 1 R P R P Active At rest Molecular hinges to control accessibility of active sites Figure 1 Molecular model of endoclucanase 12A and schematic model of the DMAAmenzyme molecular switch. The red residues represent the catalytic glutamic acid side chains at the active site of EG 12A, the green residue is the Asn 55 position, the purple residue is the Ser 25 position, and the Nterminus is represented as the blue circle. Tsuyoshi Shimoboji, Edmund Larenas, Tim Fowler, Allan S. Hoffman,* and Patrick S. Stayton* Bioconjugate Chem., 14 (3), 517 525, 2022 Figure 4 Characterization of ONPC enzyme activities for free DMAAmEG 12A conjugates in solution at as function of polymer size and conjugation site. The enzyme activities were measured for 100 nM conjugates using ONPC (8mM) as a substrate and normalized to the activity of N55C or S25C EG12A controls as 100% at each temperature. EG 12AM10, 10 kDa DMAAmEG12A conjugate。 EG 12AM6, 6 kDa DMAAmEG 12A conjugate。 EG 12AM3, 3 kDa DMAAmEG 12A conjugate。 and EG 12A + M10, physical mixture of enzyme plus 10 kDa DMAAm. Tsuyoshi Shimoboji, Edmund Larenas, Tim Fowler, Allan S. Hoffman,* and Patrick S. Stayton* Bioconjugate Chem., 14 (3), 517 525, 2022 Molecular Switching via Redox 1. Reduction by ascorbic acid 2. Oxidation with ammonium persulfate 3. Conformational change monitored by circular dichroism S. Zahn and . Canary, Angew. Chem. Int. Ed. 37 (1998) 305 V. Balzani, A. Credi, . Raymo, . Stoddart, Angew. Chemie Int. Ed. 39 (2022)3348 J. Rebek, Jr