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Nucleoside Analogues that Mimic Water in the Minor GrooveCarlson, Alena January 2012 (has links)
Thesis advisor: Larry W. McLaughlin / Hydration in the minor groove of B-form DNA influences the stability and conformation of duplex DNA. An analogue nucleoside that attempts to mimic the N3-hydrated adenine was designed and synthesized. Obtaining the modified adenine was a significant synthetic effort. The attempted incorporation of the new analogue in a DNA strand yielded inconclusive results, and further tests are ongoing. The incorporation of the new modified purine in a DNA duplex may be useful for a better understanding of the hydration of B-form DNA. / Thesis (MS) — Boston College, 2012. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.
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Synthetic studies towards the phytotoxic natural product herbicidin CMalik, Majbeen January 1997 (has links)
No description available.
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The molecular and biochemical characterisation of thymidine kinase 1 from normal and transformed mammary cell linesBritton, Fiona Catherine January 1997 (has links)
No description available.
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Design, synthesis and evaluation of nucleotides and nucleotide dimers as potential anti-HIV agentsTsang, Hing Wo January 1995 (has links)
No description available.
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The reactions of fluorinated ketonesLateef, Juma January 1999 (has links)
No description available.
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Synthetic studies on sinefunginHoward, P. N. January 1986 (has links)
No description available.
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Synthetic studies in nucleoside chemistryStewart, Alistair J. January 2003 (has links)
No description available.
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Modifying the Natural State of Nucleic Acids: Three-Dimensional DNA Lattices and Extended DeoxyribonucleosidesHardter, Eric January 2014 (has links)
Thesis advisor: Larry W. McLaughlin / By virtue of encoding and transferring hereditary information, nucleic acids effectively represent the blueprint for life as we know it. Given the biological relevance of this class of polymers, it comes as no surprise that scientists are constantly striving to reach a greater understanding of the innumerable genetic corridors contained within the human genome. This has led to the rational design and synthesis of numerous nucleoside analogues in an attempt to alter and subsequently control native nucleic acid structure and function. The first attempts at harnessing the latent abilities of DNA are described in Chapter 2. Multiple tetrahedral branching "hubs" were designed, synthesized and characterized, at which point single-stranded DNA could be elongated from each of the four points of origin. Ensuing hybridization studies were performed with the goal that the binding traits of these elongated tetrahedral lattices could be monitored, and that fully formed lattices could potentially function as means of drug encapsulation or molecular tethering. Chapter 3 describes direct alteration of the standard DNA backbone. Successive synthetic efforts towards creating a 6'-extended deoxyadenosine molecule are detailed, and its effects on the stability of duplexed DNA (along with sister molecules 6'-deoxythymidine and an elongated 3'-deoxythymidine) are also defined. Upon insertion into DNA, this class of extended nucleosides could ultimately lead to a new duplex structure, as well as novel binding properties. / Thesis (PhD) — Boston College, 2014. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.
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Novel Cyclo Deoxynucleoside: Synthesis and EvaluationYu, Hongchuan January 2012 (has links)
Thesis advisor: Larry W. McLaughlin / Thesis advisor: Mary F. Roberts / Nucleic acids are essential biological molecules for life. For example, deoxyribonucleic acid (DNA) is the main genetic information carrier; ribonucleic acid (RNA) plays a critical role in translation and transcription. These characteristics place nucleic acids as the fundamental genetic materials of a living system. Since over a century ago, intensive attempts have been made by researchers to study the nucleic acid properties. For chemists, it is particularly interesting and important to understand the relationship between structures and properties of nucleic acids. For instance chemical modifications can alter stability of nucleic acids, and consequently influence their biochemical behaviors. In this work, we began by investigation of a 5',6-cyclo-modified nucleic acid resembling the product of DNA oxidation, and then developed a library of cyclomodifications. Our research on their structures and properties indicated that by installing cyclo-modifications we might be able to add some properties, that were not observed in nature to nucleic acids. / Thesis (PhD) — Boston College, 2012. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.
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The Mechanism of Action of a New Class of Nucleoside Analogs Targeting Gastrointestinal TumoursCollins, Laura 25 February 2019 (has links)
Gastrointestinal malignancies such as liver and pancreatic cancers are the deadliest due to late detection and drug resistance. Nucleoside analogues, like Gemcitabine, are the conventional therapy despite their little impact on survival and off-target toxicity. A novel class of nucleoside analogues able to evade drug resistance mechanisms has been developed by the Guindon group and biologically screened in our lab. Some of these proprietary molecules were further equipped with a lipoate moiety designed to target cancer cell metabolism. LCB2151 and LCB2179 have emerged as the lead molecules in this class, with an IC50 of 10-15 µM in the Gemcitabine-resistant human pancreatic (Capan-2 & Panc-1) cancer cell lines. The focus of this project is deciphering the cellular mechanisms activated by LCB2151 in these pancreatic cancer lines. A series of biased molecular approaches, like gene expression profiling, and unbiased large throughput proteomic and metabolomics analyses were applied to identify potential targets and affected pathways. Results collectively show that LCB2151 evades drug resistance mechanisms, increases pro-apoptotic markers and impairs mitochondrial respiration as early as 6 hours posttreatment. Furthermore, MS/MS analyses reveal that LCB2151 alters the levels of several metabolites in the central carbon metabolism pathway and identifies the citric acid cycle enzyme α-ketoglutarate dehydrogenase as a potential molecular target of LCB2151. Understanding the exact mechanism of action of our lead molecule along with extensive testing on murine cancer models, will surely pave its way to clinical testing and evaluation.
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