Authors
|
Köhler, T. ; Patsis, P.A. ; Hahn, D. ; Ruland, A. ; Naas, C. ; Müller, M. ; Thiele, J.
|
Title
|
DNAzymes as catalysts for L-tyrosine and amyloid beta oxidation
|
Date
|
27.03.2020
|
Number
|
58563
|
Abstract
|
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.
|
Publisher
|
ACS Omega
|
Wikidata
|
|
Citation
|
ACS Omega 5 (2020) 7059-7064
|
DOI
|
https://doi.org/10.1021/ACSOMEGA.9B02645
|
Tags
|
|