Identification and Directed Development of Non-Organic Catalysts with Apparent Pan-Enzymatic Mimicry into Nanozymes for Efficient Prodrug Conversion

Raoul Walther, Anna K. Winther, Anne Sofie Fruergaard, Wouter van den Akker, Lise Sørensen, Signe Maria Nielsen, Morten T. Jarlstad Olesen, Yitao Dai, Henrik S. Jeppesen, Paolo Lamagni, Aleksandr Savateev, Søren Lykke Pedersen, Camilla Kaas Frich, Cécile Vigier-Carrière, Nina Lock, Mandeep Singh, Vipul Bansal, Rikke L. Meyer, Alexander N. Zelikin (Corresponding author)

Research output: Contribution to journalArticleAcademicpeer-review

26 Citations (Scopus)

Abstract

Nanozymes, nanoparticles that mimic the natural activity of enzymes, are intriguing academically and are important in the context of the Origin of Life. However, current nanozymes offer mimicry of a narrow range of mammalian enzymes, near-exclusively performing redox reactions. We present an unexpected discovery of non-proteinaceous enzymes based on metals, metal oxides, 1D/2D-materials, and non-metallic nanomaterials. The specific novelty of these findings lies in the identification of nanozymes with apparent mimicry of diverse mammalian enzymes, including unique pan-glycosidases. Further novelty lies in the identification of the substrate scope for the lead candidates, specifically in the context of bioconversion of glucuronides, that is, human metabolites and privileged prodrugs in the field of enzyme-prodrug therapies. Lastly, nanozymes are employed for conversion of glucuronide prodrugs into marketed anti-inflammatory and antibacterial agents, as well as “nanozyme prodrug therapy” to mediate antibacterial measures.

Original languageEnglish
Pages (from-to)278-282
Number of pages5
JournalAngewandte Chemie - International Edition
Volume58
Issue number1
DOIs
Publication statusPublished - 2 Jan 2019
Externally publishedYes

Keywords

  • enzyme mimicry
  • enzyme-prodrug therapy
  • glucuronide
  • nanozymes
  • prodrugs

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