Control of biocatalytic transformations by programmed DNA assemblies.
This study demonstrates the self-assembly of inhibitor/enzyme-tethered nucleic acid fragments or enzyme I-, enzyme II-modified nucleic acids into functional nanostructures that lead to the controlled inhibition of the enzyme or the activation of an enzyme cascade. In one system, the anti-cocaine aptamer subunits are modified with monocarboxy methylene blue (MB(+)) as the inhibitor and with choline oxidase (ChOx). The cocaine-induced self-assembly of the aptamer subunits complex results in the inhibition of ChOx by MB(+). In a further configuration, two nucleic acids of limited complementarity are functionalized at their 3' and 5' ends with glucose oxidase (GOx) and horseradish peroxidase (HRP), respectively, or with MB(+) and ChOx. In the presence of a target DNA sequence, synergistic complementary base-pairing occurs, thus leading to stable supramolecular Y-shaped nanostructures of the nucleic acid units. A GOx/HRP bienzyme cascade or the programmed inhibition of ChOx by MB(+) is demonstrated in the resulting nucleic acid nanostructures. A quantitative theoretical model that describes the nucleic acid assemblies and that results in the inhibition of ChOx by MB(+) or in the activation of the GOx/HRP cascade, respectively, is provided.
Freeman
Ronit
R
Institute of Chemistry, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.
Sharon
Etery
E
Teller
Carsten
C
Willner
Itamar
I
D052157:Aptamers, Nucleotide / Q000737:chemistry; D055162:Biocatalysis; D003124:Colorimetry; D004247:DNA / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000737:chemistry; D005949:Glucose Oxidase / Q000737:chemistry; D008751:Methylene Blue / Q000737:chemistry; D009690:Nucleic Acid Conformation
D052157:Aptamers, Nucleotide; D004791:Enzyme Inhibitors; D004247:DNA; D005949:Glucose Oxidase; D008751:Methylene Blue