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This thesis discusses two major projects. The first project focuses on understanding the effect of chirality on intrinsic acidity of oligopeptides. Gas-phase acidity (ΔacidG) and related thermochemical parameters (ΔacidH, and ΔacidS), of model N- and C-terminal cysteine polyalanine peptides in which one L-alanine was substituted by a D-alanine viz. CAADA and AADAC, were measured by the extended Cooks kinetic method. Gas-phase acidities of CAADA and AADAC were measured to be about 318 kcal/mol and 322 kcal/mol, respectively. These values are different from the gas-phase acidities of the all L-amino acid containing analogues of the above peptides, but suggest that D-alanine containing peptides show the same trend as their all L-amino acid analogues with the N-terminal cysteine peptide being more acidic than the C-terminal cysteine peptide. However, the difference in the acidities of CAADA and AADAC is about 4 kcal/mol which is about half of the difference between their all L-amino acid analogues. These results also suggest that, presumably, a single L-alanine to D-alanine substitution has a moderate effect on the conformation of the respective peptides. The aim of the second project is to understand how acidic amino acids influence peptide fragmentation during tandem mass spectrometric analysis. A series of model N- and C- terminal glutamic acid polyalanine and polyglycine (EAn, AnE (n=2,3); EGn (n=2,3), GnE (n=2-4)) and cysteine polyalanine (CAn, AnC (n=4-6)) peptides were studied. Primarily, EAn and EGn peptides formed bn ions. In contrast, while EOn peptides formed all yn ions, EAn peptides formed fewer yn ions. Similarly, AnE and GnE peptides also formed bn ions. No major differences were observed in yn ion formation. For both sets of peptides, water loss seemed to trend with the position of glutamic acid. CAn and AnC peptides also formed bn ions, just like their glutamic acid counterparts. However, yn ions were observed only for AnC peptides. For all sets of peptides, ions related to bn and yn ions were also observed.

Thesis advisor: Eranthie Weerapana / Adeno-Associated Virus (AAV) has been developed into a powerful therapeutic tool - in the last ten years it has acted as a gene-delivery vehicle in several approved therapeutics and many more therapeutics on trial. Despite extensive research, gaps in our understanding of AAV’s infectious cycle still exist, and further development is needed for the creation of improved gene therapy vectors. Technology to incorporate Unnatural Amino Acids (UAAs) into the AAV capsid has recently been developed, and could aid in both furthering our understanding of AAV’s biology and in the therapeutic advancement of AAV. In this work, we demonstrate how the functionalization of the AAV capsid using UAA incorporation can advance our control over the AAV capsid and aid in probing and manipulating AAV biology. We describe our use UAA incorporation to place a bio-orthogonal reactive handle into AAV’s capsid followed by functionalization with a targeting moiety and demonstrate the unprecedented amount of control that UAA incorporation provides in the creation of a functional virus conjugate. We are able to control both the precise placement and the stoichiometry of the targeting moiety on the AAV capsid, providing a platform that, for the first time, can undergo rigorous optimization analogous to that which medicinal chemists put small molecules through. We also describe the creation of a new platform to site-specifically modify the AAV capsid using cysteine incorporation, a technique that retains the ability to site-specifically modify the capsid as UAA incorporation does, but does not require the excess machinery that UAA incorporation requires. Next we discuss the incorporation of a photocaging amino acid, NBK, into the AAV capsid. Using NBK, we were able to effectively block AAV’s primary binding interaction with Heparan Sulfate Proteoglycan (HSPG) and control the timing of AAV infection using light to chemically remove the photo-protecting group. While photocaging the HSPG interaction is only a proof of concept, it demonstrates the remarkable amount of control that UAA incorporation affords, and lends insight to what could be accomplished using the functionalities that can be placed on the AAV capsid with UAAs. / Thesis (PhD) — Boston College, 2020. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

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Certain aspects of the biochemistry of the thyroid gland have been studied. The techniques of filter paper chromatography and radioautography were used to separate and identify the iodine-containing amino acids of the gland, and were modified somewhat, in order to obtain reliable results. Although a series of preliminary experiments were performed with the thyroid glands of rats in vivo, the main part of this work made use of the in vitro technique. Surviving tissue slices were incubated in the presence of the radioactive tracer, iodine131. Evidence was obtained which indicated that at least two of the amino acids found "free" in the thyroid gland were degraded by the gland to inorganic iodide. The mechanism of action of a number of thyroid gland inhibitors was investigated. It was found that all but two of the materials studied led to the formation in the tissue slices of unidentified iodine—containing materials with the simultaneous disappearence of inorganic iodide. Hence, at least a part of the goitrogenic nature of these inhibitors would appear to be due to the "removal" of iodide. It was found chat one portion of the inhibition caused by 3 - fluorotyrosine could be "reversed" in vitro with tyrosine, interesting sex variations in thyroid gland activity were observed during these experiments. / Thesis / Master of Science (MSc)

Background: Manufacturers have used emulsifying salts universally in the processed cheese industry since James L. Kraft patented the first processed cheese in 1916. My objective was to find alternative ingredients to replace emulsifying salts in processed cheese formulations; the product would follow "clean-labeling" trends and lower the final formulation's sodium content. Materials and Methods: My experiments followed conventional processed cheese formulations to create experimental batches, which were compared to positive and negative controls for significance. Textural, rheological, and melting tests evaluated objective cheese parameters. We observed subjective sensory properties through qualitative descriptive analysis, consumer acceptance panels, and focus groups. Results: We found that aspartic acid, cysteine, and glutamic acid could functionally emulsify a processed cheese formulation, as seen in the Manuscript section of this thesis. Potential future applications can be found under the Optimization Research section of this thesis. Conclusions: Alternative ingredients can make a large change on the processed cheese industry to improve current manufacturing practices and the nutrition of food products. While optimization work can always improve upon formulations, we propose a few formulations that could serve to replace traditional processed cheese practices.

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