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Authors
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Köhler, T. ; Patsis, P.A. ; Hahn, D. ; Ruland, A. ; Naas, C. ; Müller, M. ; Thiele, J.
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Title
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DNAzymes as catalysts for L-tyrosine and amyloid beta oxidation
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Date
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27.03.2020
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Number
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58563
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Abstract
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Single-stranded deoxyribonucleic acids have an enormous potential for catalysis by applying tailored sequences of nucleotides for individual reaction conditions and substrates. If such a sequence is guanine-rich, it may arrange into a three-dimensional structure called G-quadruplex and give rise to a catalytically active DNA molecule, a DNAzyme, upon addition of hemin. Here, we present a DNAzyme-mediated reaction, which is the oxidation of l-tyrosine toward dityrosine by hydrogen peroxide. With an optimal stoichiometry between DNA and hemin of 1:10, we report an activity of 101.2 ± 3.5 µUnits (µU) of the artificial DNAzyme Dz-00 compared to 33.0 ± 1.8 µU of free hemin. Exemplarily, DNAzymes may take part in neurodegeneration caused by amyloid beta (Aß) aggregation due to l-tyrosine oxidation. We show that the natural, human genome-derived DNAzyme In1-sp is able to oxidize Aß peptides with a 4.6% higher yield and a 33.3% higher velocity of the reaction compared to free hemin. As the artificial DNAzyme Dz-00 is even able to catalyze Aß peptide oxidation with a 64.2% higher yield and 337.1% higher velocity, an in-depth screening of human genome-derived DNAzymes may identify further candidates with similarly high catalytic activity in Aß peptide oxidation.
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Publisher
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ACS Omega
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Wikidata
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Citation
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ACS Omega 5 (2020) 7059-7064
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DOI
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https://doi.org/10.1021/ACSOMEGA.9B02645
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