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Selective Recognition Of Quadruplex Dna By Small Molecules, Elizabeth W. White Dec 2006

Selective Recognition Of Quadruplex Dna By Small Molecules, Elizabeth W. White

Chemistry Dissertations

Structure-specific recognition of nucleic acids is a promising method to reduce the size of the recognition unit required to achieve the necessary selectivity and binding affinity for small molecules. It has been demonstrated recently that G-quadruplex DNA structures can be targeted by organic cations in a structure-specific manner. Structural targets of quadruplexes include the planar end surfaces of the G-tetrad stacked columns as well as four grooves. The significant structural differences between quadruplex DNA and duplex DNA make quadruplex DNA a very attractive target for highly selective, structure-specific drug design. We have used a variety of biophysical techniques including circular …


Insights Into Sulfonated Phthalocyanines; Insights Into Anionic Tetraaryl Porphyrins; Irradiation Of Cationic Metalloporphyrins Bound To Dna, Anila Fiaz Gill Dec 2006

Insights Into Sulfonated Phthalocyanines; Insights Into Anionic Tetraaryl Porphyrins; Irradiation Of Cationic Metalloporphyrins Bound To Dna, Anila Fiaz Gill

Chemistry Dissertations

Sulfonated porphyrins and phthalocyanines have been under consideration as microbicides, compounds which, when used in a topical formulation, can prevent transmission of the human immunodeficiency virus. Our studies have been directed toward the characterization of members of these classes. For the sulfonated phthalocyanines, matrix-assisted laser desorption/ionization (MALDI) mass spectrometry was helpful in determining the extent of sulfonation. We present the first report of spectroscopic characterization of a pentasulfonated phthalocyanine. Capillary electrophoresis data were sensitive to the concentration of the compounds (Chapter 1). Mass spectrometry was also very useful for establishing the extent of sulfonation in series of sulfonated porphyrins. Capillary …


Synthesis Of Boronic Acid Based Sensors For Glucose And Sialic Acid And Synthesis Of Novel And Selective Pde4 Enzyme Inhibitors, Gurpreet Kaur Dec 2006

Synthesis Of Boronic Acid Based Sensors For Glucose And Sialic Acid And Synthesis Of Novel And Selective Pde4 Enzyme Inhibitors, Gurpreet Kaur

Chemistry Dissertations

The boronic acid functional group is known to bind compounds with the diol group tightly and reversibly in aqueous environment and has been used as a recognition moiety for the design of carbohydrate sensors. The first chapter of the dissertation studies the synthesis and substitution effect on the affinity and selectivity of a known boronic acid-based glucose sensor. In such a sensor design effort, the availability of a signaling event, whether it is fluorescence or UV, is crucial. The second chapter studies the detailed mechanism on how a well-known fluorescent boronic acid compound changes fluorescent properties upon binding. A new …


Syntheses And Dna Interactions Of Acridine And Phenothiazine Based Photosensitizers, Beth Wilson Dec 2006

Syntheses And Dna Interactions Of Acridine And Phenothiazine Based Photosensitizers, Beth Wilson

Chemistry Dissertations

Photosensitizing molecules and/or metal complexes that interact with DNA via intercalation and groove binding have potential applications as molecular structural probes, as footprinting reagents and in photodynamic therapeutics. To this regard, small molecules that bind to DNA and the energetics involved in these interactions, acridine-based therapeutics, photosensitization, photodynamic therapy, phenothiazine-mediated photosensitization, DNA photocleavage reaction mechanisms and photosensitizing metal complexes are introduced in Chapter I. Next, in Chapter II, the synthesis of a photonuclease consisting of a 3,6-acridinediamine chromophore attached to four metal-coordinating imidazole rings is described. The DNA photocleavage yields, emission quantum yields, and thermal denaturation studies by this acridine-imadazole …


Design Of Novel Molecular Micelles For Capillary Electrophoresis, Syed Asad Ali Rizvi Aug 2006

Design Of Novel Molecular Micelles For Capillary Electrophoresis, Syed Asad Ali Rizvi

Chemistry Dissertations

The research presented in this dissertation involves the synthesis, characterization, and application of novel anionic and cationic chiral molecular micelles in capillary electrophoresis (CE) for the separation of diverse chiral compounds. Chapter 1 presents brief overview of the surfactants, micelle polymer, CE and micellar electrokinetic chromatography (MEKC). Chapter 2 describes the simultaneous enantioseparation of eight single chiral center â-blockers using two novel leucine and isoleucine based polymeric surfactants. The simultaneous enantioseparation of multichiral center bearing â-blockers, nadolol and labetalol is described in chapter 3. A synergistic approach, using a combination of polysodium N-undecenoxycarbonyl-L-isoleucinate (poly-L-SUCIL) and sulfated â-CD showed dramatic enantioseparation …


Shape-Dependent Molecular Recognition Of Specific Sequences Of Dna By Heterocyclic Cations, Yi Miao Aug 2006

Shape-Dependent Molecular Recognition Of Specific Sequences Of Dna By Heterocyclic Cations, Yi Miao

Chemistry Dissertations

SHAPE-DEPENDENT MOLECULAR RECOGNITION OF SPECIFIC SEQUENCES OF DNA BY HETEROCYCLIC CATIONS by YI MIAO Under the Direction of Dr. W. David Wilson ABSTRACT DB921 and DB911 are biphenyl-benzimidazole-diamidine isomers with a central para- and meta-substituted phenyl group, respectively. Unexpectedly, linear DB921 has much stronger binding affinity with DNA than its curved isomer, DB911. This is quite surprising and intriguing since DB911 has the classical curved shape generally required for strong minor groove binding while DB921 clearly does not match the groove shape. Several biophysical techniques including thermal melting (Tm), circular dichroism (CD), biosensor-surface plasmon resonance (SPR), and isothermal titration calorimetry …


Crystallographic Analysis And Kinetic Studies Of Hiv-1 Protease And Drug-Resistant Mutants, Yunfeng Tie Jun 2006

Crystallographic Analysis And Kinetic Studies Of Hiv-1 Protease And Drug-Resistant Mutants, Yunfeng Tie

Chemistry Dissertations

HIV-1 protease is the most effective target for drugs to treat AIDS, however, the long-term therapeutic efficiency is restricted by the rapid development of drug resistant variants. To better understand the molecular basis of drug resistance, crystallographic and kinetic studies were applied to wild-type HIV-1 protease (PR) and drug-resistant mutants, PRV82A, and PRI84V, in complex with substrate analogues, the current drug saquinavir and the new inhibitor UIC-94017 (TMC-114). UIC-94017 was also studied with mutants PRD30N and PRI50V. The drug-resistant mutations V82A, I84V, D30N and I50V participate in substrate binding. Eighteen crystal structures were refined at resolutions of 0.97-1.60A. The high …


On The Mechanistic Roles Of The Protein Positive Charge Close To The N(1)Flavin Locus In Choline Oxidase, Mahmoud Ghanem Jun 2006

On The Mechanistic Roles Of The Protein Positive Charge Close To The N(1)Flavin Locus In Choline Oxidase, Mahmoud Ghanem

Chemistry Dissertations

Choline oxidase catalyzes the oxidation of choline to glycine betaine. This reaction is of considerable medical and biotechnological applications, because the accumulation of glycine betaine in the cytoplasm of many plants and human pathogens enables them to counteract hyperosmotic environments. In this respect, the study of choline oxidase has potential for the development of a therapeutic agent that can specifically inhibit the formation of glycine betaine, and therefore render pathogens more susceptible to conventional treatment. The study of choline oxidase has also potential for the improvement of the stress resistance of plant by introducing an efficient biosynthetic pathway for glycine …