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- ItemSynthesis of Enzyme Inspired Immobilized Catalysts(Auckland University of Technology, 2023) Malingin, MarcThe primary objective of this study is to develop an immobilized catalyst for transphosphorylation, drawing inspiration from enzymatic processes. To accomplish this goal, a set of key objectives were set. Firstly, the synthesis of TACN (A) and guanidinium (B) ligands is paramount. Then, the next objective is to immobilize these ligands onto a solid resin, establishing a bioactive site through a copper-catalyzed azide-alkyne cycloaddition (CuAAC) "click reaction." Lastly, the study aims to evaluate the catalytic activity of these supported catalysts using the model substrate HPNPP. This assessment seeks to identify optimal conditions for catalytic activation and to elucidate potential cooperativity in the catalytic process. The focus of this project lies in investigating the catalytic properties of the selected ligands when immobilized on solid resin as an alternative to gold nanoparticles. The investigation includes the characterization of molecules, monitoring reactions through NMR and IR spectroscopy, and evaluating catalytic activity using UV-vis spectroscopy. TACN (A) was initially synthesized using a protective group, Boc, and this was employed to selectively perform a substitution reaction at the desired site. Subsequently, "click chemistry" was utilized to attach it to the resin. Finally, the protective group was cleaved under acidic conditions. The synthesis of Guanidinium (B) was approached through three distinct routes. The first route involved a standard substitution reaction, followed by a Staudinger reduction reaction, ending in guanylation. In the second route, with the aim of enhancing efficiency and effectiveness, a different starting material was used and tosylation was performed before following the aforementioned steps. The third route employed a completely different route, employing Gabriel synthesis to obtain the amine, which was eventually subjected to guanylation. Similar to the TACN synthesis, the "click reaction" was employed to immobilize the ligands, and deprotection was achieved through acidic conditions. We successfully showcased the immobilization of different functional groups onto the Merrifield resin's surface, resulting in the creation of a highly efficient transphosphodiesterase. This achievement holds promise for applications in synthesizing artificial enzymes characterized by great stability compared to their biological counterparts, along with the convenience of recovery and reusability. Our future research endeavors will focus on further enhancing this technology by exploring combinations of the two existing ligands and potentially introducing additional ligands in varying proportions, with the aim of developing artificial enzymes boasting even greater catalytic activities.
- ItemA Qualitative Study Examining the Opinions and Experiences of New Zealand Participants Regarding Beliefs of Sugar as an Addictive Substance(Auckland University of Technology, 2023) Rosser, AlexandraThe present study aims to examine New Zealand participants’ perceptions of sugar as an addictive substance. The concept of sugar addiction is not new and there has already been some research around this, however due to ethical implications in human research, most studies have used animal experiments. Despite the myriad of health concerns caused by sugar overindulgence, including diabetes, obesity, cardiovascular disease, stroke, cancer, tooth decay and other issues, we do not yet have a conclusive answer as to the validity of sugar addiction. This study asked participants to draw from their understanding and experiences of sugar to explain whether they believed it should be classified as addictive. Qualitative content analysis was used to draw meaning and context from the rationale described by participants. Both inductive and deductive methods were used to determine whether perceptions and experiences by individuals in this study aligned with established scientific criteria surrounding substance dependence. For a considerable majority, signs and symptoms relating to excessive sugar intake conformed to current understandings of addiction. Conversely, those who did not believe sugar was addictive referenced how various biopsychosocial influences may contribute to sugar overindulgence, highlighting the complex nature of sugar consumption. While relying exclusively on subjective measures has inherent limitations, understanding individual experiences with sugar is essential in comprehending how a range of factors may shape indulgence. Given the consistency between participant experiences of sugar addiction and scientific literature concerning substance dependence, further measures should be implemented in evaluating the credibility of sugar as an addictive substance.
- ItemSynthesis and Antibiotic Activity of Vitamin B12-Vancomycin Conjugates(Auckland University of Technology, 2023) Stackpole, BenVitamin B12 has the potential to be used as a “Trojan horse” for drug delivery applications, with previously reported examples including anti-cancer drugs and antimicrobial drugs. As B12 is too large to cross cellular membranes by diffusion, humans and bacteria uptake it via active transport processes mediated by a series of proteins. Conjugating therapeutic molecules to B12 allows this process to be hijacked to transport cargo into cells. Because B12 is an essential nutrient and many species of bacteria cannot synthesise it themselves, this is a promising method for transporting antibiotics into bacteria. This may be especially useful in the case of Gram-negative bacteria, which possess an additional outer membrane that prevents many antibiotics from entering the cell. In this research project, we investigated the antibiotic activity of B12-vancomycin conjugates. Vancomycin is a glycopeptide antibiotic which inihibits bacterial cell wall synthesis. Due to its large size, it cannot diffuse across bacterial membranes and so it is only effective against Gram-positive bacteria. By conjugating vancomycin to B¬12, we hypothesised that it could be transported across the outer membrane of Gram-negative bacteria and inhibit their growth. Four different B12-vancomycin conjugates were successfully synthesised, differing in the linker used and the site of conjugation to B12. The conjugates were tested for antibiotic activity against Escherichia coli. None of the conjugates displayed antibiotic activity.
- ItemThe Design and Synthesis of Light Responsive GSK-3 Inhibitors(Auckland University of Technology, 2023) Clotworthy, MeganThe inhibition of kinase enzymes has proven to be a valuable therapeutic approach for the treatment of various diseases (such as cancer, cellular metabolism and neurodegenerative disorders). Despite the large number of potent kinase inhibitors reported in the literature, many of these typically bind to multiple kinase targets and exhibit poor tissue selectivity, giving rise to undesired side effects. The idea of creating selective drugs has proven difficult, as once a drug is administered, there is very little control over when and where the drug is active within a biological system. The implementation of photopharmacology (the use of light to control the biological activity of a drug) into drug design and development could prove to be useful in developing molecular tools with improved tissue selectivity. Through the use of photocages, known drugs can be modified to be inactive. Only once administered to the cellular setting is the caged inhibitor exposed to a selected wavelength of light, liberating the active form of the drug at the desired target. This project focusses on the development of photocaged glycogen synthase kinase 3 (GSK-3) inhibitors through the introduction of fluorescent caging groups onto a key binding moiety. This project firstly entails the successful synthesis of a known GSK-3
- ItemSurvey Study of Challenging and Mystical Experiences After Consuming Psilocybin Mushrooms in New Zealand(Auckland University of Technology, 2023) Zong, Zixuan (Jonathan)Background: Psilocybin is a psychedelic substance which is contained within certain species of mushrooms. Research has identified that in addition to the acute psychedelic effects of psilocybin, there are longer-lasting consequences of psilocybin consumption, including change in personality, and reduction in depressive symptoms and substance use disorder. However, little research has investigated the acute and lasting effects of psilocybin consumption in the New Zealand population. Aim: The present study aims to explore the extent of mystical experiences, meaningfulness, spiritual significance, and enduring changes in wellbeing resulting from recreational psilocybin experiences, and how these factors are affected by difficult or challenging experiences. Method: A quantitative anonymous survey was distributed online by convenience sampling and was open between August 31, 2022 to November 5, 2022. 511 New Zealanders completed the survey. Participants completed the Mystical Experience Questionnaire 30 (MEQ30) and survey questions about the difficulty, meaningfulness, spiritual significance, and enduring changes to wellbeing as a result of the psilocybin experience. Participants could also provide open-ended written comments about their experience. Results: Participants reported high levels of mystical experiences (MEQ30 Total Average = 99.3), with 36.2% achieving Complete Mystical Experiences. High levels of meaningfulness, spiritual significance, enduring positive changes in wellbeing due to the psilocybin experience were also found, with a moderate number of participants having a challenging psilocybin experience. A Spearman’s rho correlation analysis showed significant positive correlations between all previously mentioned factors with a p < .001, except for the relationship between the estimated psilocybin dosage and enduring changes in wellbeing (p < .01), difficulty and enduring changes in wellbeing (p < .01), and between difficulty and positive mood (not significant). A slight difference was found between participants who achieved a Complete Mystical Experience, and those who did not. Conclusion: This study provided an initial insight into the recreational psilocybin experiences of people in New Zealand, looking at the relationship between psilocybin experiences, challenging or otherwise, and their impact on personal meaning, spiritual significance, and enduring changes in wellbeing. The findings are consistent with prior research, indicating that both mystical and challenging experiences of higher intensity are associated with greater increases in personal meaning, spiritual significance, and lasting improvements in wellbeing.