Nucleic Acids, Nucleotides, and Nucleosides Commons^™

Development Of A Microwave-Based Dna Extraction Method To Increase The Success Of Direct And Rapid Pcr Technique, Fabiana Taglia

FIU Electronic Theses and Dissertations

The goal of this project was to develop a fast, microwave-based extraction technique that could be employed for direct and rapid DNA analysis. The hypothesis was that the use of a microwave could increase the yield of DNA by opening the cell membrane, rendering the DNA available without the use of any other chemical treatment, and improving results from very low quantity samples.

At present rapid human DNA analysis is mainly restricted to genotyping saliva and sometimes blood samples. We hypothesized that microwave processing could expand the types of samples assessable to these procedures and increase sensitivity.

There were two …

Nucleoside Analogues For Positron Emission Tomography Imaging And To Study Radiation Mediated Generation Of Radicals From Azides, Maria E. De Cabrera

FIU Electronic Theses and Dissertations

Gemcitabine is a potent anticancer cytidine analogue used to treat solid tumors. Its efficacy is diminished by rapid deamination to a toxic uridine derivative by cytidine deaminase. To overcome this limitation and add radioactive nuclei (¹⁸F or ⁶⁸Ga) for PET imaging, I synthesized two 4-N­-alkylgemcitabine analogues i) bearing β-keto tosylate moiety for subsequent ¹⁸F-fluorination and ii) having SCN-Bn-NOTA chelator to complex ⁶⁸Ga. The first was synthesized by replacement of tosylamide in 4-N­-tosylgemcitabine with 1-amino-10-undecene, followed by elaboration of terminal alkene through dihydroxylation, regioselective tosylation and oxidation. Subsequent fluorination using KF in …

Azido- And Triazolyl-Modified Nucleoside/Tide Analogues: Chemistry, Fluorescent Properties, And Anticancer Activities, Zhiwei Wen

FIU Electronic Theses and Dissertations

Two classes of C5 azido-modified pyrimidine nucleosides were synthesized and explored as radiosensitizers. The 5-azidomethyl-2'-deoxyuridine (AmdU) was prepared from thymidine and converted to its cytosine counterpart (AmdC). The 5-(1-azidovinyl) modified 2'-deoxyuridine (AvdU) and 2'-deoxycytidine (AvdC) were prepared employing regioselective Ag-catalyzed hydroazidation of 5-ethynyl pyrimidine substrates with TMSN₃. AmdU and AmdC were converted to 5'-triphosphates AmdUTP and AmdCTP, and incorporated into DNA-fragments via polymerase-catalyzed reaction during DNA replication and base excision repair. Radiation-mediated prehydrated electrons formed in homogeneous aqueous glassy (7.5 M LiCl) systems in the absence of oxygen at 77 K led to site-specific formation of π-type aminyl …

Epigenetic Instability Induced By Dna Base Lesion Via Dna Base Excision Repair, Zhongliang Jiang

FIU Electronic Theses and Dissertations

DNA damage can cause genome instability, which may lead to human cancer. The most common form of DNA damage is DNA base damage, which is efficiently repaired by DNA base excision repair (BER). Thus BER is the major DNA repair pathway that maintains the stability of the genome. On the other hand, BER mediates DNA demethylation that can occur on the promoter region of important tumor suppressor genes such as Breast Cancer 1 (BRCA1) gene that is also involved in prevention and development of cancer. In this study, employing cell-based and in vitro biochemical approaches along with bisulfite DNA sequencing, …

Design And Synthesis Of Novel Nucleoside Analogues: Oxidative And Reductive Approaches Toward Synthesis Of 2'-Fluoro Pyrimidine Nucleosides, Ramanjaneyulu Rayala

FIU Electronic Theses and Dissertations

Fluorinated nucleosides, especially the analogues with fluorine atom(s) in the ribose ring, have been known to exert potent biological activities. The first part of this dissertation was aimed at developing oxidative desulfurization-fluorination and reductive desulfonylation-fluorination methodologies toward the synthesis of 2'-mono and/or 2',2'-difluoro pyrimidine nucleosides from the corresponding 2'-arylthiopyrimidine precursors. Novel oxidative desulfurization-difluorination methodology was developed for the synthesis of α,α-difluorinted esters from the corresponding α-arylthio esters, wherein the arylthio group is present on a secondary internal carbon. For the reductive desulfonylation studies, cyclic voltammetry was utilized to measure the reduction potentials at which the sulfone moiety of substrates can …

Design And Synthesis Of 4-N-Alkanoyl And 4-N-Alkyl Gemcitabine Analogues Suitable For Positron Emission Tomography, Jesse E. Pulido

FIU Electronic Theses and Dissertations

Gemcitabine is a highly potent chemotherapeutic nucleoside agent used in the treatment of several cancers and solid tumors. However, it is therapeutically limitated because of toxicity to normal cells and its rapid intracellular deamination by cytidine deaminase into the inactive uracil derivative. Modification at the 4-(N) position of gemcitabine's exocyclic amine to an -amide functionality is a well reported prodrug strategy which has been that confers a resistance to intracellular deamination while also altering pharmacokinetics of the parent drug. Coupling of gemcitabine to carboxylic acids with varying terminal moieties afforded the 4-N-alkanoylgemcitabines whereas reaction of 4-N …