DNAzymes as Catalysts for L-Tyrosine and Amyloid β Oxidation

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 mu Units (mu U) of the artificial DNAzyme Dz00 compared to 33.0 +/- 1.8 mu U of free hemin. Exemplarily, DNAzymes may take part in neurodegeneration caused by amyloid beta (A beta) aggregation due to L-tyrosine oxidation. We show that the natural, human genome-derived DNAzyme In1-sp is able to oxidize A beta 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 A beta 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 A beta peptide oxidation.