Tailoring Protein–Polymer Conjugates as Efficient Artificial Enzymes for Aqueous Asymmetric Aldol Reactions

Abstract

Artificial enzymes are becoming a powerful toolbox for selective organic syntheses. Herein, we first propose an advanced artificial enzyme by polymeric modularity as an efficient aldolase mimic for aqueous asymmetric aldol reactions. Based on an in-depth understanding of the aldolase reaction mechanism and our previous work, we demonstrate the modular design of protein−polymer conjugates by co-incorporating L-proline and styrene onto a noncatalytic protein scaffold with a high degree of controllability. The tailored conjugates exhibited remarkable catalytic performance toward the aqueous asymmetric aldol reaction of p-nitrobenzaldehyde and cyclohexanone, achieving 94% conversion and excellent selectivity (95/5 diastereoselectivity, 98% enantiomeric excess). In addition, this artificial enzyme showed high tolerance against extreme conditions (e.g., wide pH range, high temperature) and could be reused for more than four times without significant loss of reactivity. Experiments have shown that the artificial enzyme displayed broad specificity for various aldehydes.

Artificial Biocatalysis: Quo Vadis?

“…[63] The ArPoly platform allows further tuning of the polymer chain, e. g. by introduction of hydrophobic moieties leading to increased reactivity and selectivity. [64] In addition, the L-proline moiety in the polymer side chain can coordinate copper(II) ions leading to an ArPoly generating an artificial clickase for alkyne-azide coupling. This clickase converted several alkynes and azides completely to the corresponding triazols at a low catalyst loading of 0.157 mol % (referring to the copper content).…”

“…The change of the protein scaffold to BSA improved the performance of the ArPoly and up to 65 % conversion and 99 % ee were achieved with different arylaldehyde aldol acceptors [63] . The ArPoly platform allows further tuning of the polymer chain, e. g. by introduction of hydrophobic moieties leading to increased reactivity and selectivity [64] . In addition, the L‐proline moiety in the polymer side chain can coordinate copper(II) ions leading to an ArPoly generating an artificial clickase for alkyne‐azide coupling.…”