TY - JOUR
T1 - Identification and Directed Development of Non-Organic Catalysts with Apparent Pan-Enzymatic Mimicry into Nanozymes for Efficient Prodrug Conversion
AU - Walther, Raoul
AU - Winther, Anna K.
AU - Fruergaard, Anne Sofie
AU - van den Akker, Wouter
AU - Sørensen, Lise
AU - Nielsen, Signe Maria
AU - Jarlstad Olesen, Morten T.
AU - Dai, Yitao
AU - Jeppesen, Henrik S.
AU - Lamagni, Paolo
AU - Savateev, Aleksandr
AU - Pedersen, Søren Lykke
AU - Frich, Camilla Kaas
AU - Vigier-Carrière, Cécile
AU - Lock, Nina
AU - Singh, Mandeep
AU - Bansal, Vipul
AU - Meyer, Rikke L.
AU - Zelikin, Alexander N.
PY - 2019/1/2
Y1 - 2019/1/2
N2 - 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.
AB - 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.
KW - enzyme mimicry
KW - enzyme-prodrug therapy
KW - glucuronide
KW - nanozymes
KW - prodrugs
UR - http://www.scopus.com/inward/record.url?scp=85057456567&partnerID=8YFLogxK
U2 - 10.1002/anie.201812668
DO - 10.1002/anie.201812668
M3 - Article
C2 - 30408323
AN - SCOPUS:85057456567
VL - 58
SP - 278
EP - 282
JO - Angewandte Chemie - International Edition
JF - Angewandte Chemie - International Edition
SN - 0570-0833
IS - 1
ER -