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STRUCTURAL STUDY OF THE N6-(DEOXY-D-ERYTHRO-PENTOFURANOSYL)-2,6- DIAMINO-3,4-DIHYDRO-4-OXO-5-N-METHYLFORMAMIDO-PYRIMIDINE DNA ADDUCTDempster, Richard Kenichi 24 December 2014 (has links)
N6-(Deoxy-d-erythro-pentofuranosyl)-2,6-diamino-3,4-dihydro-4-oxo-5-N-methylformamidopyrimidine (MeFapy-dG) is the methylated and persistent ring opened product of the common N7 alkylation site of guanines in DNA, formed upon the subsequent addition of hydroxide to C8. Depending on the sequence, MeFapy-dG has been shown to block DNA polymerases and cause both transversion and deletion mutations during replication. It is an important adduct to study due to its persistence and mutagenicity, but has not been looked into extensively because of the lack of synthetic availability. Recently, Professor Carmelo J. Rizzo and co-workers at Vanderbilt University developed a novel synthetic method for the incorporation of the MeFapy-dG adduct into oligonucleotides, which allowed examination of potential conformations and anomers of the MeFapy-dG adduct within a particular oligonucleotide sequence via nuclear magnetic resonance spectroscopy.
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Studies in diethyl quinolate.Dennis, Donald Albert. January 1952 (has links)
The object of this investigation was firstly to compare the three methods for the preparation of quinolinic acid (pyridine 2,3-dicarboxylic acid), namely, the oxidation of quinoline in a water solution either by potassium permanganate or hydrogen peroxide and the oxidation of 8-hydroxy quinoline with nitric acid at low temperatures. The first method seemed to be the most desirable since quinoline from coal-tar is an inexpensive material and potassium permanganate costs less than hydrogen peroxide. Previous publications dealing with this oxidation give low and inconsistent yields. Therefore, it was of interest to improve the method of oxidation of quinoline with potassium permanganate. The other problem in this research was to study the condensation of diethyl quinolate and ethyl acetate with basic catalysts in order to obtain derivatives of the pyrindene series.
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Bio-Imprinted Hydro-Gels (BIGs) for Protein and Virus Detection.Bai, Wei 07 May 2014 (has links)
Detection of bio-markers at low concentration is becoming a more and more important topic in scientific research due to its importance in applications crucially related to peoples life like medical diagnosis, environment protection and national security.
In the past decades, as the improvement of the modern analytical technologies progressed, plenty of methodologies have been developed to realize the fast and accurate detection of bio-markers in liquid media. However, some drawbacks still remain like the expensive cost, high requirement of operational environment, and need for skilled operators.
Here, a new kind of aptamer-based bio-imprinted hydrogel sensor (BIG) with specific macroscopic volume response to certain biomarkers like proteins and virus at low concentration is reported.
These super-aptamer hydrogels exhibit macroscopic volume change that can be detected by naked eyes when being treated with bio-marker solutions at extremely low concentration. This extraordinary macromolecular amplification is attributed to a complex interplay between biomarker-aptamer crosslinks and the structure of the hydrogel network surrounding it.
Additionally, based on the work mentioned above, a new kind of bio-imprinted grating hydrogel film which can show visible change of the laser diffraction pattern when treated with biomarker solutions was also designed and fabricated based on the super-aptamer bioimprinted hydrogels. These films have also been proved to be able to detect both proteins and virus at low concentration in solutions.
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Advancing Quantitative Structure Activity Relationship Strategies in Ligand-Based Computer-Aided Drug DesignButkiewicz, Mariusz 28 July 2014 (has links)
Quantitative structure activity relationship (QSAR) modeling using high-throughput screening (HTS) data enables the development of predictive models for in silico screening. A cheminformatics framework termed BCL::ChemInfo was developed to establish QSAR modeling for application in drug discovery. Its prediction performance was evaluated through an extensive benchmark study assessing curated datasets from PubChem. BCL::ChemInfo was applied to identify novel pathway specific inhibitors for β-hematin crystallization in Plasmodium falciparum associated with Malaria. The resulting models achieved an experimental enrichment of 44 fold compared to the initial HTS hit rate of 0.37% for compounds based on a concentration threshold of 70µM. Sampled from these identified hit compounds, 15 out of 17 molecules were confirmed to perturb the hemozoin formation pathway in P. falciparum. Another research study involved the identification of novel specific allosteric modulators for mGlu5 acting on a distinct site related to CPPHA binding. From a compound library of over four million commercially available compounds five compounds where identified through in silico screening and experimentally validated to bind exclusively to this novel site. BCL::ChemInfo was also adapted to predict small molecule properties such as the wateroctanol partition coefficient (LogP). The resulting prediction accuracy surpassed the current gold standard method XLogP.
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Reductive Alkylation of Proteins Towards Structural and Biological ApplicationsRoberson, Kevin Jerome 29 July 2014 (has links)
Nuclear magnetic resonance (NMR) spectroscopy is a proven technique for protein structure and dynamic studies, typically requiring the incorporation of stable magnetic isotopes to improve sensitivity and assign resonances. Degenerate levels of 13C-incorporation have been the biggest obstacle for mass spectrometry-assisted assignment of 13C-dimethylamine resonances in nuclear magnetic resonance spectroscopy (NMR). Reductive 13C-methylation is an alternative labeling method for proteins not amenable to bacterial host overexpression. Because reductive 13C-methylation adds sparse, isotopic labels, traditional methods of assigning the NMR signals are not applicable. The research presented in the first part of this dissertation explores several methods used to break the degeneracy in 13C-labeling of lysozyme. To overcome the degeneracy in labeling lysozyme with the reductive methylation reaction, we investigated two methods: 1) reductive methylation in the presence of 18-crown-6-ether (18C6) and 2) reductive methylation using multiple reducing agents. To assign the - and -dimethylamine resonances of the N-terminal lysine residue of lysozyme, a non-destructive Edman degradation method was explored. The second part of this research discusses an alternative assignment method based on mass spectrometry to aid in the assignment of the NMR signals from reductively 13C-methylated proteins. Because assignment is increasingly difficult when lysine is the N-terminal residue of the protein, one method is described to identify the NMR resonance of the 13C-methyls associated with both the N-terminal α-amine and the side chain ε-amine. The NMR signals of the N-terminal α-dimethylamine and the side chain ε-dimethylamine of hen egg white lysozyme Lys1 are identified in 1H-13C heteronuclear single-quantum correlation spectra. Protein chemical modification is a well-established field that continues to impact leading research today including glycomimetics and cross-linking of proteins. Current protein chemical modifications like polyethylene glycol are proven useful for increasing the lifetime of several therapeutic enzymes but are also toxic to the body. In the last chapter, we present the use of sugar derivatives as a possible less toxic alternative for synthetic glycoproteins. The synthesis of a protein modifier is described and preliminary data of its application as a glycomimetic and cross-linking agent is presented.
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GOLD MONOLAYER-PROTECTED CLUSTERS FUNCTIONALIZED WITH PEPTIDIC ANTI-HEMAGGLUTININ PARATOPESBryant, Matthew Vann 29 July 2014 (has links)
Analysis of crystal structures of native antibodies bound to the hemagglutinin (HA) surface receptor of influenza have provided pertinent chemical information and metrics of the antibody-antigen interactions at the complimentary determining region (CDR) and receptor-binding domain (RBD) interface. We proposed that using this information, we could design a gold monolayer-protected cluster (AuMPC) functionalized with peptidic anti-HA paratopes and determine equilibrium rate constants of this particle-protein interaction. The peptidic ligands incorporate thiol surface modulators, polyethylene glycol spacing module, and specificity through a molecular recognition element (MRE). The MRE will be based upon the amino acid sequences of CDRs of specific antibodies to HA of pandemic influenza virus. Bio-layer interferometry experiments were conducted with these AuMPCs to determine equilibrium rate constants. The modular design of our ligands coupled with our platform made for an interdisciplinary and novel approach to nanoparticle biomimetics.
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Synthesis and properties of some novel conducting polymersPrevost, Adeline January 2002 (has links)
No description available.
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Luminescent materials based on Lanthanide ionsSudhakaran Pillai, S. January 2010 (has links)
The inclusion of lanthanide (III) (Ln[sup]3+) ions into polymers by “covalent” bonding has applications. Heteroleptic hydrotris(pyrazolyl)borate crotonate and cinnamate complexes were synthesised for reasons that, firstly, knowledge of the polymerisable double bond was helpful in establishing the conditions of any copolymerisation reaction; secondly, the chosen ligands are very good at receiving energy in the UV region; and thirdly, lanthanide complexes might undergo changes in properties, on moving between adjacent lanthanide ions, allowing potentially convenient isolations of pure materials at the monomer production stage, or even at the polymerisation stage. For both complexes, two classes of target complex were identified: the mononuclear (Er-Lu) and dinuclear (La-Ho). Mononuclear forms were identified by MS, [sup]1H NMR and elemental analysis and dinuclear forms were characterised by X-ray crystallography. For heteroleptic hydrotris(pyrazolyl)borate crotonate and cinnamate complexes, the ligands act as antennae for receiving and then transferring energy to metal ions and these complexes were studied in several homogeneous and heterogeneous copolymers as well as in rigid PMMA or polystyrene matrices. Luminescence decay of these complexes depends on the distance between the metal and C-H oscillators so the cinnamate complexes showed better luminescence life-times compared to crotonate complexes. The copolymer system helped to reduce the concentration quenching compared to corresponding metal complex / polymer blend systems. The thermal stabilities of the complex monomers were increased by incorporating them into polymer chains. Europium crotonate and cinnamate complexes in the poly(p-phenylenevinylene) (PPV) precursor blends showed the characteristic emission of europium, and the emission from PPV was quenched by increasing the europium content in the PPV precursor blends.
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On the theory of Chemical CombinationBrown, Alexander Crum January 1861 (has links)
This paper was presented in 1861 to the Faculty of Medicine, when I was a candidate for the degree of M.D. In consequence of a somewhat adverse opinion expressed as to the speculations contained in it, I exercised the discretion allowed (I think unwisely) by the University to graduates, and did not print it. Some of my friends have urged me to do so now, and although I am quite aware that it contains much that is crude and some things that are erroneous, and that all that was then new or important in it has since been much better expressed by others, I still think that it is not altogether unworthy of preservation as a contribution to the history of the subject. It is printed verbatim, and I would ask such of my friends as may read it to recollect that it was written eighteen years ago by a medical student. A. C. B. University Of Edinburgh, March 1879.
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N-Donor Ligands as Potential Linkers For BioconjugationLewis, Nerissa Abigail 11 April 2017 (has links)
The potential application of metals in medicine is enormous. This study explores the fundamental chemistry directed at the eventual use of novel Re, Pt, and B12-conjugates with potential application for targeted delivery of metal-containing therapeutic and diagnostic agents. This study explores two different approaches that could be used in bioconjugation.
The first approach employs the use of the cyclic C2-symmetrical amine, 1-(4-pyridyl)piperazine, to form new amidine complexes, fac-[Re(CO)3(Me2bipy)(HNC(CH3)(pyppz))]BF4. Such amidine complexes have an exposed, highly basic pyridyl nitrogen that readily coordinates to the cobalt atom in a simple B12 model, (py)Co(DH)2Cl (DH = monoanion of dimethylglyoxime), producing dinuclear fac-[Re(CO)3(Me2bipy)(u-(HNC(CH3)(pyppz)))Co(DH)2Cl]BF4 complexes. The present goal was to provide guidance for the development of 99mTc and 186/188Re radiopharmaceuticals for targeted tumor imaging and therapy. 1H NMR spectroscopic analysis of all compounds and single-crystal X-ray crystallographic data for selected complexes established that the amidine had only the E configuration in both the solid and solution states, and that the pyridyl group is bound to Co in the respective dinuclear complexes. We anticipate that our method of employing a coordinate bond for conjugating the fac-[ReI(CO)3] core to a vitamin B12 model could be extended to natural B12 derivatives. Such an approach is a very attractive method for the development of 99mTc and 186/188Re radiopharmaceuticals for targeted tumor imaging and therapy since B12 compounds are known to accumulate in cancer cells.
I extended this chemistry to include new pyppzSO2R ligands (R = Me Me2Nnap = 5-(dimethylamino)naphthyl)), and 3,5-Me2C6H3 = 3,5-dimethylphenyl) bearing sulfonamide sulfonamide links. The novel pyppzSO2R ligands are very good donors that bind very strongly to the respective Re or Co metal centers; a feature that is necessary for our bioconjugation approach. Treatment of fac-[ReI(CO)3(Me2bipy)(CH3CN)]BF4 and (Cl or CH3)Co(DH)2(py) (DH = monoanion of dimethylglyoxime) with these sulfonamide ligands afforded the respective fac-[ReI(CO)3(Me2bipy)(pyppzSO2R)]BF4, (CH3)Co(DH)2(pyppzSO2R), and (Cl)Co(DH)2(pyppzSO2R) complexes. These ligands and compounds are characterized by NMR spectroscopy and X-ray crystallography.
In the second approach we synthesized new trans-[PtII(4-Xpy)2Cl2] and [PtII(4-Xpy)4]Cl2 complexes bearing 4-substituted pyridines (4-Xpy) with limited volatility and water solubility; properties typical of 4-Xpy with X being a moiety targeting drug delivery. The high solubility of [PtII(4-Xpy)4]Cl2 salts in CDCl3 as well as the very downfield shift of [PtII(4-Xpy)4]Cl2 H2/6 signals indicated that the ion pairs are stabilized by CHCl contacts. Furthermore, crystal structures of the [PtII(4-Xpy)4]Cl2 salts confirmed that the chloride ions occupy a pseudo axial position with non bonding (py)C-HCl distances well within the range of a typical CHCl H-bonding contacts. Our synthetic and spectroscopic results can be readily extended to other non-volatile ligands.
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