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Synthesis and Polymerase-Mediated Transcription of Base-Modified 2’-Fluoroarabinose Nucleic Acid in Preparation for Particle Display Selection with Modified Aptamers:Skrodzki, Christopher J. A. January 2019 (has links)
Thesis advisor: Jia Niu / Nucleic acid aptamers are promising alternatives to antibodies for a wide array of diagnostic and therapeutic applications. However, state-of-the-art aptamers suffer from poor pharmacokinetics and diversity, limiting their affinity and specificity for many therapeutically relevant targets. The emerging field of glycoscience provides opportunities to improve the utility of aptamers over antibodies. Combining synthetic chemistry with modern molecular biology and polymer science, the synthesis of Xeno Nucleic Acid monomers and chemoenzymatic polymerization via engineered polymerase enzymes allows the production of nucleic acid drugs with superior resistance to endogenous nucleases. The modular structure of nucleic acids provides for the design of sequence defined polymers capable of post-synthetically appending complex synthetic glycans, extending the catalytic geometry of aptamers. Our SELEX inspired FACS based particle display approach allows for high-throughput screening. Additionally, we expect this method has the capability of screening aptamers in human serum. Our synthetic approach utilizes a Sonogashira cross-coupling reaction to install a flexible alkyne to the major groove of 2′-deoxy-2′-fluoro-arabinose uracil base. By incorporated recent advances in nucleic acid synthesis, one-pot nucleobase activation and sugar glycosylation is achieved and bis-oxybenzyl phosphoamidite synthesis can afford gram scale HPLC-free purification of the triphosphates. The FANA C8-alkyl-uridine triphosphate will be incorporated by an engineered Tgo DNA polymerase to allow systematic introduction of alkynyl conjugation handles into a DNA-templated FANA polymer. Subsequent conjugation with azido-modified glycans via the Huisgen coppercatalyzed alkyne-azide cycloaddition (CuAAC) click reaction will generate sequence controlled nucleic acid-carbohydrate hybrid molecules amendable for directed evolution. / Thesis (MS) — Boston College, 2019. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.
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A facile screening strategy to construct auto-fluorescent protein-based biosensors / 蛍光タンパク質を利用したバイオセンサーの効率的な構築法に関する研究Tajima, Shunsuke 23 March 2022 (has links)
京都大学 / 新制・課程博士 / 博士(エネルギー科学) / 甲第23998号 / エネ博第434号 / 新制||エネ||82(附属図書館) / 京都大学大学院エネルギー科学研究科エネルギー基礎科学専攻 / (主査)教授 森井 孝, 教授 片平 正人, 教授 佐川 尚 / 学位規則第4条第1項該当 / Doctor of Energy Science / Kyoto University / DFAM
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New high through-put assays for detecting transglutaminase activityBen Tahar, Wajih January 2008 (has links)
Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal.
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New high through-put assays for detecting transglutaminase activityBen Tahar, Wajih January 2008 (has links)
Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal
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