Rational design of allosteric switchable catalysts

Abstract

Allosteric regulation, in many cases, involves switching the activities of natural enzymes, which further affects the enzymatic network and cell signaling in the living systems. The research on the construction of allosteric switchable catalysts has attracted broad interests, aiming to control the progress and asymmetry of catalytic reactions, expand the chemical biology toolbox, substitute unstable natural enzymes in the biological detection and biosensors, and fabricate the biomimetic cascade reactions. Thus, in this review, we summarize the recent outstanding works in switchable catalysts based on the allosterism of single molecules, supramolecular complexes, and self-assemblies. The concept of allosterism was extended from natural proteins to polymers, organic molecules, and supramolecular systems. In terms of the difference between these building scaffolds, a variety of design methods that tailor biological and synthetic molecules into controllable catalysts were introduced with emphasis.

Keywords: allosterism; molecular machine; self‐assembly; supramolecular catalysis; switchable catalyst.

SCHEME 1

(A) The activity of natural enzymes is strictly controlled by allosteric regulation. (B) Artificial switchable catalysts have been designed by incorporating catalytically active groups in allosteric scaffolds

FIGURE 1

(A) NMR structure of the CaM F92E. (B) Allosteric regulation of the CaM based catalyst. Adapted with permission.^{[ 68 ]} Copyright 2011, Wiley‐VCH

FIGURE 2

(A) Reversible switching of an artificial selenoenzyme based on the allosteric protein recoverin incorporated with selenocysteine as the active center. (B‐i) The significant difference between the catalytic curves of Ca²⁺‐free and Ca²⁺‐bound seleno‐recoverin‐Q50R. (B‐ii) Reversible switch of the selenoenzyme upon calcium ions. Adapted with permission.^{[ 69 ]} Copyright 2014, Wiley‐VCH

FIGURE 3

(A) Light‐driven molecular motor for asymmetric catalysis of Michael addition. (B) The relative rates and enantiomeric ratio of product formation for the three catalysts (P,P)‐trans‐1, (M,M)‐cis‐1, and (P,P)‐cis‐1. Adapted with permission.^{[ 75 ]} Copyright 2011, American Association for the Advancement of Science

FIGURE 4

(A) Catalytic assemblies constructed by tellurium‐containing supra‐amphiphiles. Adapted with permission.^{[ 82 ]} Copyright 2010, Wiley‐VCH. (B‐i) The morphology could be regulated between nanotubes and nanospheres. (B‐ii) A reversible switch of peroxidase activity by tube‐sphere transformation at two different temperatures. Adapted with permission.^{[ 83 ]} Copyright 2014, the American Chemical Society

FIGURE 5

(A) Acid‐base switching of a rotaxane catalyst by alternating the preferential binding site of the macrocycle. Adapted with permission.^{[ 84 ]} Copyright 2012, Wiley‐VCH. (B) Switchable catalysis of Michael addition and Diels–Alder reactions by in situ generations of a trityl cation via bromide abstraction using Zn(II)–pentafoil knot [Zn₅2](BF₄)₁₀. Adapted with permission.^{[ 86 ]} Copyright 2016, The Nature Publishing Group

FIGURE 6

(A‐i) A model of an allosteric supramolecular triple‐layer complex for the regulation of the catalytic living polymerization of є‐caprolactone. (A‐ii) catalytic activities of semiopen and closed states in the polymerization of ε‐caprolactone. Adapted with permission.^{[ 89 ]} Copyright 2010, American Association for the Advancement of Science. (B‐i) Allosteric regulation of a light‐harvesting antenna/reaction center mimic. (B‐ii) Catalytic reduction of methyl viologen in the presence of (1–3)‐ImC₆₀. (I) turning excitation source on, (II) addition of acetonitrile, (III) addition of chloride, and (IV) addition of Tl. Adapted under the terms of the Creative Commons CC BY license.^{[ 90 ]} Copyright 2015, The Nature Publishing Group

FIGURE 7

Controllable antioxidant system based on the reversible self‐assembly of SP1 with PD5. Adapted with permission.^{[ 94 ]} Copyright 2020, The American Chemical Society

FIGURE 8

(A‐i) The scheme of Q11H and Q11R co‐assembly to form amyloid‐like nanofibers. (A‐ii) Catalytic reaction rates for hydrolysis of pNPA vs molar ratio of Q11R to Q11H. Adapted with permission.^{[ 96 ]} Copyright 2014, The American Chemical Society. (B‐i) The pH‐switched artificial hydrolase based on conformational change of VK2H and the cartoon structure of the bilayer. (B‐ii) Catalytic rate of VK2H nanofibers at different pH versus the initial catalytic rate of VK2H fibrils at pH 9.5 and the on‐off switch of catalytic activity of VK2H peptide by a change in pH between 6.0 and 9.0. Adapted with permission.^{[ 97 ]} Copyright 2017, Wiley‐VCH