title: Nucleoapzymes: Hemin/G-Quadruplex DNAzyme-Aptamer Binding Site Conjugates with Superior Enzyme-like Catalytic Functions.
abstract: A novel concept to improve the catalytic functions of nucleic acids (DNAzymes) is introduced. The method involves the conjugation of a DNA recognition sequence (aptamer) to the catalytic DNAzyme, yielding a hybrid structure termed "nucleoapzyme". Concentrating the substrate within the "nucleoapzyme" leads to enhanced catalytic activity, displaying saturation kinetics. Different conjugation modes of the aptamer/DNAzyme units and the availability of different aptamer sequences for a substrate provide diverse means to design improved catalysts. This is exemplified with (i) The H2O2-mediated oxidation of dopamine to aminochrome using a series of hemin/G-quadruplex-dopamine aptamer nucleoapzymes. All nucleoapzymes reveal enhanced catalytic activities as compared to the separated DNAzyme/aptamer units, and the most active nucleoapzyme reveals a 20-fold enhanced activity. Molecular dynamics simulations provide rational assessment of the activity of the various nucleoapzymes. The hemin/G-quadruplex-aptamer nucleoapzyme also stimulates the chiroselective oxidation of L- vs D-DOPA by H2O2. (ii) The H2O2-mediated oxidation of N-hydroxy-L-arginine to L-citrulline by a series of hemin/G-quadruplex-arginine aptamer conjugated nucleoapzymes.
authors.affiliation: Institute of Chemistry, The Minerva Center for Biohybrid Complex Systems, and The Center for Nanoscience and Nanotechnology, The Hebrew University of Jerusalem , Jerusalem 91904, Israel.
authors.forename: Eyal
authors.initials: E
authors.lastname: Golub
authors.affiliation: Institute of Chemistry, The Minerva Center for Biohybrid Complex Systems, and The Center for Nanoscience and Nanotechnology, The Hebrew University of Jerusalem , Jerusalem 91904, Israel.
authors.forename: H Bauke
authors.initials: HB
authors.lastname: Albada
authors.affiliation: Institute of Chemistry, The Minerva Center for Biohybrid Complex Systems, and The Center for Nanoscience and Nanotechnology, The Hebrew University of Jerusalem , Jerusalem 91904, Israel.
authors.forename: Wei-Ching
authors.initials: WC
authors.lastname: Liao
authors.affiliation: Institute of Chemistry, The Minerva Center for Biohybrid Complex Systems, and The Center for Nanoscience and Nanotechnology, The Hebrew University of Jerusalem , Jerusalem 91904, Israel.
authors.forename: Yonatan
authors.initials: Y
authors.lastname: Biniuri
authors.affiliation: Institute of Chemistry, The Minerva Center for Biohybrid Complex Systems, and The Center for Nanoscience and Nanotechnology, The Hebrew University of Jerusalem , Jerusalem 91904, Israel.
authors.forename: Itamar
authors.initials: I
authors.lastname: Willner
mesh_terms: D052157:Aptamers, Nucleotide / Q000737:chemistry*; D001665:Binding Sites; D002384:Catalysis; D021881:DNA, Catalytic / Q000737:chemistry*; D054856:G-Quadruplexes; D006427:Hemin / Q000737:chemistry*
chemical_list: D052157:Aptamers, Nucleotide; D021881:DNA, Catalytic; D006427:Hemin