During the twentieth century in the United States, Alfred Day Hershey studied phages, or viruses that infect bacteria, and experimentally verified that genes were made of deoxyribonucleic acid, or DNA. Genes are molecular, heritable instructions for how an organism develops. When Hershey started to study phages, scientists did not know if phages contained genes, or whether genes were made of DNA or protein. In 1952, Hershey and his research assistant, Martha Chase, conducted phage experiments that convinced scientists that genes were made of DNA. For his work with phages, Hershey shared the 1969 Nobel Prize in Physiology or Medicine with Max Delbrück and Salvador Luria. Hershey conducted experiments with results that connected DNA to the function of genes, thereby changing the way scientists studied molecular biology and the development of organisms.
In 1944, Oswald Avery, Colin MacLeod, and Maclyn McCarty published an article in which they concluded that genes, or molecules that dictate how organisms develop, are made of deoxyribonucleic acid, or DNA. The article is titled “Studies on the Chemical Nature of the Substance Inducing Transformation of Pneumococcal Types: Induction of Transformation by a Desoxyribonucleic Acid Fraction Isolated from Pneumococcus Type III,” hereafter “Transformation.” The authors isolated, purified, and characterized genes within bacteria and found evidence that those genes were made of DNA and not protein. Though scientists were initially skeptical that genes were made of DNA, they later recognized that the data reported in “Transformation” were clear evidence that DNA was genetic material, a revelation that furthered research about how organisms grow, develop, and pass on traits to offspring.
In April 1953, James Watson and Francis Crick published “Molecular Structure of Nucleic Acids: A Structure of Deoxyribose Nucleic Acid” or “A Structure for Deoxyribose Nucleic Acid,” in the journal Nature. In the article, Watson and Crick propose a novel structure for deoxyribonucleic acid or DNA. In 1944, Oswald T. Avery and his group at Rockefeller University in New York City, New York published experimental evidence that DNA contained genes, the biological factors called genes that dictate how organisms grow and develop. Scientists did not know how DNA’s function led to the passage of genetic information from cell to cell, or organism to organism. The model that Watson and Crick presented connected the concept of genes to heredity, growth, and development. As of 2018, most scientists accept Watson and Crick’s model of DNA presented in the article. For their work on DNA, Watson and Crick shared the 1962 Nobel Prize in Physiology or Medicine with Maurice Wilkins.
Chapter 1 covers the research under Dr. Levitus. Four oligonucleotides were reacted for zero, five, and thirty minutes with uracil-DNA glycosylase and subsequent addition of piperidine. These oligonucleotides were chosen based on their torsional rigidities as predicted by past research and predictions. The objective was to better understand the relationship between the sequence of DNA surrounding the incorrect base and the enzyme’s ability to remove said base in order to prepare the DNA for the next step of the base excision repair pathway. The first pair of oligonucleotides showed no statistically significant difference in enzymatic efficiency with p values of 0.24 and 0.42, while the second pair had a p value of 0.01 at the five-minute reaction. The second pair is currently being researched at different reaction times to determine at what point the enzyme seems to equilibrate and react semi-equally with all sequences of DNA.
Chapter 2 covers the research conducted under Dr. Chaput. Along the TNA synthesis pathway, the nitrogenous base must be added to the threofuranose sugar. The objective was to optimize the original protocol of Vorbrüggen glycosylation and determine if there were better conditions for the synthesis of the preferred regioisomer. This research showed that toluene and ortho-xylene were more preferable as solvents than the original anhydrous acetonitrile, as the amount of preferred isomer product far outweighed the amount of side product formed, as well as improving total yield overall. The anhydrous acetonitrile reaction had a final yield of 60.61% while the ortho-xylene system had a final yield of 94.66%, an increase of approximately 32%. The crude ratio of preferred isomer to side product was also improved, as it went from 18% undesired in anhydrous acetonitrile to 4% undesired in ortho-xylene, both values normalized to the preferred regioisomer.