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1	DNA Photocleavage by Acridine and Phenazine-Based Chromophores Fields, Earl John 04 December 2006 (has links) Photodynamic therapy (PDT) is a promising approach used in the treatment of cancer, age related macular degeneration, psoriasis, and other diseases. Our research is focused on the discovery of new photonucleases for use in PDT. This study evaluates the photo-induced DNA cleaving abilities of a series of acridine and phenazine-based chromophores. The extended, aromatic ring systems of these compounds are expected to intercalate between adjoining base pairs in the DNA double-helix. Once irradiated, strand breakage, or nicking of plasmid DNA is achieved at micromolar concentrations of compound (pH 7.0 and 22 °C). Our scavenger experiments show that this process occurs as a result of direct electron transfer to oxygen and/or by means of energy transfer which results in the production of singlet oxygen. Three of the photonucleases being examined were designed to chelate metal. These exhibited increased levels of DNA photocleavage in the presence of copper(II). Photodynamic therapy Georgia State University Jr. Earl Fields Graduate office Thesis Phenazine Acridine Photocleavage Intercalator
2	OXIDATION OF NUCLEIC ACIDS: CHEMISTRY OF PURINE QUINONES AND DEVELOPMENT OF NOVEL PHOTOOXIDIZING AGENTS Komarov, Dmitry Yurievich 12 November 2010 (has links) No description available. Chemistry oxopurines 8-oxoadenosine 8-oxoinosine cross-linking dihydrodioxins photooxidizing agents DNA intercalator
3	Synthesis and applications of novel resorcin[4]arene cavitands Leaym, Xiaoxuan January 1900 (has links) Doctor of Philosophy / Department of Chemistry / Stefan Bossmann / A series of methylene-bridged resorcin[4]arenes featuring electrochemically active and hydrophilic viologene-units chemically attached to their "rim"-regions have been synthesized. Depending on the choices of pendent groups (feet) and the numbers of positive charges on the "rim" (four or eight), moderate to very good solubilities in water were obtained. A fluorescent coumarin tag designed for the purpose of photophysical studies was chemically linked to the feet of some of the synthesized resorcin[4]arenes. These compounds were designed to act as guests in mycobacterial channel proteins (channel blockers). The proven host-guest interaction between resorcin[4]arenes and the mycobacterial porin MspA suggests potential application of my research in TB treatment. Both, hydrophilic nutrients and metabolites have to diffuse through the porin channels of mycobacteria because of the lack of an active transport mechanism. If these channels are successfully blocked, the mycobacteria have either to synthesize new channels, which make their outer membrane more susceptible to conventional antibiotics, or they become dormant. (3,3'-dimethyl)-4,4'-bipyridinium units are very suitable electron relays. They can be reduced stepwise to viologen monoradical cations and then to uncharged viologen diradicals which possess highly negative redox potentials, allowing them to reduce C-Cl bonds. Therefore, the deep cavitand viologen resorcin[4]arenas, are expected to bind and detoxify chlorinated hydrocarbons by reductive dechlorination. In this work, the step wise reduction process of viologen- resorcin[4]arenes and the formation of negative redox potentials of double-reduced viologen resorcin[4]arenes are demonstrated by electrochemistry studies. These results encourage future studies toward an efficient electrocatalytic system for the reductive dehalogenation of organic compounds. Besides highly charged resorcin[4]arene cavitands, the synthesis of a thiol-footed resorcin[4]arene was also attempted. The product was used for gold nanoparticle binding studies. The results of the photochemistry measurements provided a proof-of-concept for using the emission of gold nanoparticles in chemical sensors after covering their surfaces with thiol-footed resorcin[4]arenes. Two heterocylic resorcin[4]arene cavitands were synthesized for DNA-intercalation studies. The results of the photochemical measurements suggested binding between DNA and the heterocyclic resorcin[4]arenes and provided proof-of-principle for potential drug applications of this type of macrocycle. Resorcinarene TB_Channel Blocker Supramolecular Chemistry Physical Organic Chemistry Organic Synthesis DNA-Intercalator Chemistry, Organic (0490) Chemistry, Pharmaceutical (0491) Chemistry, Physical (0494)
4	STUDIES ON THE SIZE AND NON-PLANARITY OF AROMATIC STACKING MOIETY ON CONFORMATION SELECTIVITY AND THERMAL STABILIZATION OF G-QUADRUPLEXES Singh, Mandeep 01 January 2020 (has links) (PDF) Targeting DNA has the advantage over proteins for cancer remediation because of the fewer copies of the ligands required for the desired therapeutic effect. Traditionally, covalent DNA binders like alkylating agents have been used to induce genetic instability through the formation of DNA lesions and strand breaks, leading to cellular apoptosis. The primary drawback of this treatment is the non-specific binding that affects both cancerous and non-cancerous cells. G-quadruplexes are the DNA secondary structures that are present in abundance near the promoter regions of the oncogenes and are involved in the regulation of their activities. A ligand-mediated stabilization of G-quadruplexes in the promoter regions and down-regulation of the associated oncogenes have been validated. In contrast to alkylating agents, G-quadruplex ligands induce genetic stabilization through non-covalent interactions. They can be designed to interact specifically with G-quadruplex DNA over duplex DNA, which reduce side effects arising from the off-targeting. G-quadruplex ligands invariably have the large planar aromatic moiety to interact with G-quadruplexes through π- π stacking interactions. For determining the size effect of the aromatic moiety on stabilization of G-quadruplexes, a series of ligands were synthesized by conjugating nucleobases or 1,10-phenanthroline with an aminoglycoside, neomycin. The resulting conjugates increased the binding affinity synergistically and enabled us to study the effect of the stacking moiety required for G-quadruplex stabilization. Nucleobase-neomycin conjugates did not show stabilization stabilize of human telomeric G-quadruplex. 1,10-Phenanthroline-neomycin conjugate (7b) on the other hand binds to human telomeric G-quadruplex with a Ka of (8.92.4)×108 M-1 and inhibits telomerase activity at 1.56 µM probably through G-quadruplex stabilization. Moving forward, we further enlarged the aromatic moiety by tethering two 1,10-phenantholine molecules together through a five-atom linker. The resulting molecule (2-Clip-phen) was conjugated with various amino-containing side chains. 2-Clip-phen derivatives showed at least 30 times weaker binding to duplex DNA over G-quadruplex DNA. In addition, compounds showed a preference for the antiparallel G-quadruplex conformation over parallel and hybrid G-quadruplex conformations, as shown in the CD spectroscopy studies. Ligands 11 and 13 induced the formation of an antiparallel G-quadruplex from random coils and stabilize it to 60 oC (Tm) in a salt-free condition. Mass spectrometry study showed the formation of a two-tetrad G-quadruplex with the 2-Clip-phen ligand. Docking study showed that the ligand interacts most favorably with antiparallel G-quadruplex conformation, which is supported further by the larger thermal stabilization effect on antiparallel G-quadruplex compared with other G-quadruplex conformations. Our study suggests that 2-Clip-phen can be used as a scaffold for designing G-quadruplex binding ligands that preferentially bind to antiparallel G-quadruplexes, which has never been reported before. 2-CP = 2-Clip-phen CD = Circular dichroism G4 = G-quadruplex ITC = Isothermal titration calorimetry Organic chemistry Pharmaceutical sciences Chemistry Medicinal and Pharmaceutical Chemistry Medicinal-Pharmaceutical Chemistry Medicine and Health Sciences Organic Chemistry Pharmacy and Pharmaceutical Sciences Physical Sciences and Mathematics
5	Darstellung und Verwendung von Nucleolipiden zur Lipophilisierung von Nucleinsäuren sowie deren Wechselwirkung und Duplex-Bildung an horizontalen Lipid-Bilayers und Phasengrenzen zur Entwicklung einer neuartigen RNA/DNA-Analytik / Synthesis and Application of Nucleolipids for the Lipophilization of Nucleic Acids and Their Interaction and Duplex Formation at Horizontal Lipid-Bilayers and Phase Boundaries for the Development of a Novel RNA/DNA Analytics Werz, Emma 17 February 2016 (has links) Ziel der vorgestellten Arbeit war die Synthese von Nucleolipiden zur Lipophilisierung von Oligonucleotiden sowie deren Untersuchung im Hinblick auf ihre Wechselwirkung und Duplex-Bildung an horizontalen Lipidmembranen und verschiedenen Phasengrenzen zur Entwicklung eines neuartigen Bio-Chips für die RNA/DNA-Analyse. Mit der Synthese N(3)-prenylierter und 2’,3’-O-ketalisierter Pyrimidinbasen Uridin und Methyluridin wurden Nucleolipid-Bausteine dargestellt, die auch als terminale Kopfgruppen eines Oligonucleotid-Dodecamers den lipophilen Charakter dieser Oligonucleotid-Sequenz erhöhten. Für den Einsatz solcher LONs (Lipo-Oligonucleotide) in einer vereinfachten RNA/DNA-Analytik wurde eine Vielzahl von Lipo-Oligonucleotiden mit diversen Nucleolipid-Kopfgruppen synthetisiert und auf ihr Einlagerungsverhalten in künstliche Lipid-Bilayer untersucht. Fluoreszenz-spektroskopische Untersuchungen zeigten, dass alle Lipo-Oligonucleotide in der Lage sind, sich in künstliche Lipid-Bilayer einzulagern. Abhängig von der Struktur, der Länge und der Anzahl der C-Atom-Ketten dieser lipophilen Anker-Bausteine wurden die Geschwindigkeit und die Festigkeit der Verankerung im Lipid-Bilayer beeinflusst. Des Weiteren wurde die Hybridisierung von LONs mit komplementären Oligomeren an Lipidmembranen untersucht. Es konnte gezeigt werden, dass die im Bilayer verankerten Lipo-Oligonucleotide mit komplementären Oligomeren DNA-Duplexe bilden. Die hybridisierte DNA wurde nicht nur über einen kovalent gebundenen Cy5-Fluorophor am Gegenstrang nachgewiesen, sondern auch über den DNA-Interkalator SYBR Green I (SG). Am Beispiel von zwei Lipo-Oligonucleotiden (LON 20 und 23), die sich schnell und fest in der Bilayermembran verankern, konnte eine spontane Akkumulation dieser LONs an CHCl3/H2O sowie H2O/n-Decan Grenzflächen direkt nach der Probenzugabe beobachtet werden. Diese und andere Ergebnisse stützen den Einsatz von Lipo-Oligonucleotiden als Ziel-Oligomere in einem neuartigen RNA/DNA-Nachweisverfahren an Phasengrenzen. Lipid-Bilayer FCS Lipo-Oligonucleotide Fluoreszenz lipophilisierte DNA Akkumulation Phasengrenzen Diffusionskoeffizient Nucleolipide SYBR Green I Lipophilie DNA-Duplex Diffusionszeit DNA-Interkalator Cy5 DNA-Duplex-Bildung DNA duplex formation Alkylierung 2`,3`-O-Ketale Farnesyl LONs lipid-bilayer FCS lipo-oligonucleotides fluorescence lipophilized DNA accumulation phase boundaries diffusion coefficient nucleolipids SYBR Green I lipophilicity DNA duplex diffusion time DNA intercalator Cy5 alkylation 2`,3`-O-ketals farnesyl LONs 35.78 - Lipide 42.12 - Biophysik 35.65 - Nukleinsäuren 35.66 - Terpene, Steroide, Alkaloide ddc:540 ddc:570

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