Electrosynthesis of mussel-inspired adhesive polymers as a novel class of transient enzyme stabilizers

Tilmann J Neubert; Maximilian M Hielscher; Keven Walter; Carolin M Schröter; Marion Stage; Ruben R Rosencrantz; Felix Panis; Annette Rompel; Kannan Balasubramanian; Siegfried R Waldvogel; Hans G Börner

doi:10.1002/anie.202419684

Electrosynthesis of mussel-inspired adhesive polymers as a novel class of transient enzyme stabilizers

Angew Chem Int Ed Engl. 2025 Jan 2:e202419684. doi: 10.1002/anie.202419684. Online ahead of print.

Affiliations

¹ Humboldt-Universität zu Berlin: Humboldt-Universitat zu Berlin, Department of Chemistry, GERMANY.
² Johannes Gutenberg Universität Mainz: Johannes Gutenberg Universitat Mainz, Electrochemistry, GERMANY.
³ Fraunhofer Institute for Applied Polymer Research: Fraunhofer-Institut fur Angewandte Polymerforschung IAP, Life Science & Bioprocesses, GERMANY.
⁴ Fraunhofer Institute for Applied Polymer Research: Fraunhofer-Institut fur Angewandte Polymerforschung IAP, Chemistry, GERMANY.
⁵ University of Virginia, Institut für Biophysikalische Chemie, AUSTRIA.
⁶ University of Vienna: Universitat Wien, Institut für Biophysikalische Chemie, AUSTRIA.
⁷ Karlsruhe Institute of Technology: Karlsruher Institut fur Technologie, Institute of Biological and Chemical Systems - Functional MolecularSystems (IBCS-FMS), GERMANY.
⁸ Humboldt-Universitat zu Berlin, Department of Chemistry, Brook-Taylor-Str. 2, 12489, Berlin, GERMANY.

PMID: 39743873
DOI: 10.1002/anie.202419684

Abstract

Multifunctional ortho-quinones are required for the formation of thiol-catechol-connectivities (TCC) but can be delicate to handle. We present the electrochemical oxidation of the dipeptide DiDOPA, achieving up to 92% conversion efficiency of the catechols to ortho-quinones. Graphite and stainless steel could be employed as cost-efficient electrodes. The electrochemical activation yields quinone-solutions, which are free of undesired reactive compounds and eliminates the challenging step of isolating the reactive quinones. The DiDOPA quinones were employed in polyaddition reactions with multi-thiols, forming oligomers that functioned as transient enzyme stabilizers (TES). These TCC-TES-additives improved the thermal stability and the activity of tyrosinase in heat stress assays.

Keywords: Electrosynthesis; PEGylation; Protein engineering; green chemistry; peptide adhesives.