The topological diversity of DNA G-quadruplexes may play a crucial role in its biological function. Reversible control over a specific folding topology was achieved by the synthesis of a chiral, glycol-based pyridine ligand and its fourfold incorporation into human telomeric DNA by solid-phase synthesis. Square-planar coordination to a Cu ion led to the formation of a highly stabilizing intramolecular metal-base tetrad, substituting one G-tetrad in the parent unimolecular G-quadruplex. For the Tetrahymena telomeric repeat, Cu -triggered switching from a hybrid-dominated conformer mixture to an antiparallel topology was observed. Cu -dependent control over a protein-G-quadruplex interaction was shown for the thrombin-tba pair (tba=thrombin-binding aptamer).
The enzymatic synthesis of terpenes was investigated by using a cascade based on the mevalonic acid pathway. Suitable enzymes from all kingdoms of life were identified and combined to give rise to geosmin and patchoulol as representative compounds. The pathway was studied in three separate segments, which were subsequently combined in a ten-step cascade plus added cofactor regeneration systems. The cascade delivers farnesyl pyrophosphate with >40 % conversion and cyclises it to sesquiterpenes with >90 % conversion.
3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase was investigated in different organic cosolvents by means of kinetic and calorimetric measurements, molecular dynamics simulations, and small-angle X-ray scattering. The combined experimental and theoretical techniques were essential to complement each other's limitations in the investigation of the complex interaction pattern between the enzyme, different solvent types, and concentrations. In this way, the underlying mechanisms for the loss of enzyme activity in different water-miscible solvents could be elucidated. These include direct inhibitory effects onto the active center and structural distortions.
Die topologische Diversitätv on DNA-G-Quadruplexen scheint eine entscheidende Rolle füri hre biologische Funktion zu spielen. Reversible Kontrolle über eine spezifische Faltungstopologie wurde durch die Synthese eines chiralen Glykol-basierten Pyridylliganden und dessen vierfachen Einbau in eine menschliche Telomersequenz über DNA-Festphasensynthese erreicht. Die quadratisch-planare Koordination eines Cu II -Ions führte zur Bildung einer stark stabilisierenden intramolekularen Metallbasen-Tetrade,w elched ie Position einer G-Tetrade aus dem zugrundliegenden unimolekularen G-Quadruplex einnimmt. Fürd ie telomerischeW iederholungseinheit aus der Gattung Tetrahymena wurde eine Cu IIinduzierte Schaltung von einer Hybrid-dominierten Konformermischung zu einer antiparallelen Topologie beobachtet. Cu II -abhängige Kontrolle über eine Protein-G-Quadruplex-Wechselwirkung konnte fürd as Thrombin-Thrombinbindungsaptamer-Paar gezeigt werden.
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