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Modifying the Natural State of Nucleic Acids: Three-Dimensional DNA Lattices and Extended Deoxyribonucleosides

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.

Identiferoai:union.ndltd.org:BOSTON/oai:dlib.bc.edu:bc-ir_103610
Date January 2014
CreatorsHardter, Eric
PublisherBoston College
Source SetsBoston College
LanguageEnglish
Detected LanguageEnglish
TypeText, thesis
Formatelectronic, application/pdf
RightsCopyright is held by the author, with all rights reserved, unless otherwise noted.

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