Protein Modifications: From Chemoselective Probes to Novel Biocatalysts

Abstract

Chemical reactions can be performed to covalently modify specific residues in proteins. When applied to native enzymes, these chemical modifications can greatly expand the available set of building blocks for the development of biocatalysts. Nucleophilic canonical amino acid sidechains are the most readily accessible targets for such endeavors. A rich history of attempts to design enhanced or novel enzymes, from various protein scaffolds, has paved the way for a rapidly developing field with growing scientific, industrial, and biomedical applications. A major challenge is to devise reactions that are compatible with native proteins and can selectively modify specific residues. Cysteine, lysine, N-terminus, and carboxylate residues comprise the most widespread naturally occurring targets for enzyme modifications. In this review, chemical methods for selective modification of enzymes will be discussed, alongside with examples of reported applications. We aim to highlight the potential of such strategies to enhance enzyme function and create novel semisynthetic biocatalysts, as well as provide a perspective in a fast-evolving topic.

Catalase‐functionalized ZnO and graphene oxide used as electrocatalyst for the selective detection of hydrogen peroxide

“…28 It boosts catalytic and electrochemical properties while also providing biocompatibility. [29][30][31] The electrochemical H 2 O 2 biosensors found in recent literature generally do not show high sensitivity and have very low stability. These biosensors struggle to maintain a consistent sensor response for more than a week.…”

The Evolving Nature of Biocatalysis in Pharmaceutical Research and Development

“…Several excellent reviews have been published on industrial biocatalysis covering various aspects of enzymatic transformations for drug development. ,,− As such, this perspective does not aim to be comprehensive but rather highlight the current state-of-the-art of preparative enzymatic synthesis in an industrial setting. Therefore, the use of biocatalysis for small-scale pharmaceutical metabolite synthesis, lead diversification, ,,, bioconjugation, and selective protein modification − will not be focused upon in this article.…”

Enzyme‐Polymer Conjugates for Tuning, Enhancing, and Expanding Biocatalytic Activity

“…Several reports have demonstrated that the modification of the surface of functional proteins can modulate their native activity [5–7] . The modification of the primary sequence of the protein can give rise to several scenarios: from the complete inactivation of the protein to a significant enhancement of its performance.…”

“…[3,4] Several reports have demonstrated that the modification of the surface of functional proteins can modulate their native activity. [5][6][7] The modification of the primary sequence of the protein can give rise to several scenarios: from the complete inactivation of the protein to a significant enhancement of its performance. Among all the combinations of functional proteins and artificial materials, the particular case of enzymes modified with polymers requires detailed investigation.…”