No description available.

No description available.

No description available.

Thesis advisor: Larry W. McLaughlin / Nucleic acids are responsible for maintaining the biological information responsible for the activities of all known living organisms. Research of nucleic acids provides opportunities to help understand, prevent, and cure disease in addition to allowing us to gain a greater appreciation for the wonders of nature. This work presents the synthesis and properties of several modified nucleosides. Chapter 2 presents an improved synthesis of R and S 6,5'-cyclouridine, which are rigidified nucleosides locked in the anti conformation. This work helps to understand the properties of these interesting molecules and will allow scientists to synthesize large quantities of these monomers for future research. Chapter 3 presents the synthesis of novel 6,6'-(S)-cyclo-2'-deoxyuridine. This work is highlighted by a zinc mediated cyclization to form a seven-membered ring; the first published reaction of its kind. The compound itself is a mimic of thymidine that also has the base locked in the anti position. Lastly, Chapter 4 presents work on 6' extended backbone nucleosides. These molecules have the potential to form a new type of helical structure and will help us to gain a greater understanding of the properties and dynamics that contribute to duplex stability in DNA. / Thesis (PhD) — Boston College, 2012. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

It has recently been shown that the binding site of SAHase, an enzyme critical in the replication mechanism of viruses, is quite flexible and exhibits a large difference between the "open" and "closed" conformations, thus presenting an obstacle towards design efforts. As a possible solution to this dilemma, we have strategically designed and synthesized a series of structurally innovative nucleosides possessing a heteroaromatic purine ring split into its two components (for example, an imidazole and pyrimidine ring), thereby conferring additional degrees of conformational freedom and torsional flexibility to the ligand. As a result, these molecular "chameleons" can adapt to the environment of the flexible binding site in order to maximize and complement structural interactions, without losing the integrity of the crucial contacts involved in the enzyme's mechanism of action. The synthesis of several proximal analogues is presented herein.

The design and optimization of chemotherapeutic molecules through molecular modeling is a rapidly growing aspect of drug design. The recent increase in computer power and accompanying decrease in the cost of hardware has led to the wide use of computational chemistry in the development of new drugs. In addition, virtual screening of compound libraries also aids in the rapid development of new drugs. In that regard, there are three computational projects in addition to a project involving the synthesis of potential inhibitors that compile the research presented herein. The first project involves molecular mechanics simulations of isoadenosine analogues as potential inhibitors of S-adenosylhomocysteine hydrolase (SAHase). These analogues possess a carbocyclic moiety at the N-3 position instead of the normal N-9. The second project involves molecular mechanics simulations on flexible nucleosides as bioprobes of biologically significant enzymes. These purine analogues have nucleobases that are separated into their imidazole and pyrimidine rings connected by a single carbon-carbon bond.. This feature imparts flexibility to the base. The third project involves molecular dynamics simulations on expanded purine nucleotides in modified DNA. These compounds possess a heteroaromatic spacer ring inserted between the imidazole and pyrimidine portions of adenosine and guanosine purine rings. These analogues were and are incorporated into 10- and 20-mer DNA strands to investigate the effects on DNA. The final project focuses on the synthesis of a series of chlorinated 3-deazaadenosine analogues as potential anticancer agents. These 3-deazaadenine analogues have chlorine systematically placed in the 2-, 6- and 8-positions of adenine.

Typescript (photocopy) / 164 leaves : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.)--University of Adelaide, Dept. of Physical and Inorganic Chemistry, 1982

Thesis (Ph.D.)--University of Nebraska-Lincoln, 2007. / Title from title screen (site viewed Dec. 4, 2007). PDF text: x, 362 p. : ill. ; 13 Mb. UMI publication number: AAT 3271933 . Includes bibliographical references. Also available in microfilm and microfiche formats.

Dissertation (Ph.D.)--Auburn University, 2005. / Abstract. Vita. Includes bibliographic references.

Diss. (sammanfattning) Uppsala : Sveriges lantbruksuniv., 2006. / Härtill 4 uppsatser.