Master Degree / Yüksek Lisans Tezleri

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2002 - 200912020 - 20232

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Language: search.filters.language.enSubject: search.filters.subject.HIV (Viruses)

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  • Master Thesis
    Bioinformatic Approaches To Investigate Hiv Capsid-Nanobody Interaction
    (01. Izmir Institute of Technology, 2023) Atik, Şeref Berk; Taşkent Sezgin, Hümeyra
    Infection with HIV is still a global pandemic. Since the discovery of this highly mutagenic virus, nearly 40 million people have passed away as a result of HIV-related health problems. Currently, 38.4 million people are HIV-positive. Following infection, the viral genome gets integrated into the host cell genome. The infected person carries the virus for the rest of their life and can spread it to others through bodily fluids. Because there is no treatment for HIV, the World Health Organization recommends that infected people be diagnosed early through comprehensive screening to restrict the virus's spread. As a result, there is still a need to create practical, sensitive diagnostic tools, particularly for use in the field of HIV infection testing. In this study, the interaction between HIV-1 capsid protein, the first antigen found in the blood during the acute phase of HIV infection, and a nanobody (Nb, a single domain antibody) known to bind to capsid is investigated at the molecular level through computational methods. Because the structure of HIV-1 CA binding-Nb is unknown, all-atom models of the Nb structure were constructed using comparative methods, deep-learning-based methods, and hybrid methods (SwissModel, trRosetta, Robetta, AlphaFold2), and promising models were chosen. In the second stage, molecular docking was used to produce HIV-1 capsid- nanobody complex structures, which were then tested for stability and native-likeness using standard molecular dynamics simulations. Understanding the molecular details of the HIV-1 capsid-nanobody complex, we believe, will provide essential data for using this antigen-antibody pair inan immunosensor system for HIV-1 infection diagnosis.
  • Master Thesis
    Investigation of the Interaction and Olgiomerization of Hiv Capsid and Single Domain Antibody as a Biotechnological Drug Against Hiv
    (Izmir Institute of Technology, 2022) Güney, Seniha; Taşkent Sezgin, Hümeyra
    Human immunodeficiency virus (HIV) causes AIDS which is still a global public health threat. Current drugs against HIV infection cannot eradicate the virus therefore, research on new drug targets continues. HIV capsid protein, which has a highly conserved sequence and is sensitive to mutations, has critical roles in the virus lifecycle, making it a high-potential drug target. A nanobody is the antigen-binding domain of heavy-chain only antibodies of camelids. Small size, thermal stability and ease of production makes nanobodies ideal antibody fragments for therapeutic and diagnostic purposes. In the literature, a nanobody binding to the HIV-1 capsid-N terminal domain (NTD) has been reported. The aim of this thesis is to examine the potential of this nanobody as a biotechnological drug candidate against the HIV-1 and HIV-2 capsid proteins. In the study, HIV-1 capsid was expressed, purified and biophysically characterized. Thermal and chemical denaturation of the protein were done, the melting temperature and unfolding free-energy values of the protein were determined. In-vitro oligomerization of the HIV-1 capsid was performed and observed that the protein self-oligomerized over time. Pure HIV-2 capsid protein could not be produced recombinantly. Thereupon, HIV1 capsid-NTD and HIV-2 capsid-NTD proteins were expressed and purified. Secondary structure of HIV-1 capsid, HIV-1 capsid-NTD and nanobody were analyzed with circular dichroism (CD) spectroscopy and the results matched with the literature. Isothermal titration calorimetry (ITC) experiments were done to examine the HIV-1 capsidnanobody interaction, but good binding was not observed between the two proteins. Future work requires repeating ITC experiments.
  • Master Thesis
    The Effects of Newly Synthesized Compounds on the Hiv-1 Reverse Transcriptase and Blood Cells
    (Izmir Institute of Technology, 2002) Yılmazer, Özgür; Güneş, Hatice
    Acquired Immunodeficiency Syndrome (AIDS) is a result of replication of Human Immunodeficiency Virus (HIV-1) in an infected host. Reverse transcriptase (RT) enzyme of HIV-1 is a multifunctional enzyme in the life cycle of the virus. Even though many compounds have been developed against different aspects of HIV-1, RT enzyme is a prime target for the development of drugs against HIV-1 because eucaryotic cells do not have RT activity. In order to develop new therapeutic agents against HIV-1, nineteen newly synthesized compounds were analyzed for their effects on inhibition of RT activity as well as their effects on viability, proliferation, and activity of peripheral blood mononuclear cells (PBMC). Finally, mutagenic effects of the compounds were investigated. Results indicated that AVM 002 and AVM 014 were the most promising compounds with 51% and 43% inhibitory effects, respectively on RT enzyme at 100.M concentration. The compounds AVM 001, AVM 010, AVM 011, AVM 015 and AVM 019 also showed inhibitory effects between 24% and 40% at 100.M concentration.AVM 002 did not cause any toxic effect on cell viability, proliferation and activation until 500.M concentration. Similar to AVM 002, AVM 014 did not show any toxic effect on the cell viability until 500.M and 1000.M at the and of 24 hour incubation; however, AVM 014 at 500.M and 1000.M resulted in 2-fold decrease in the cell viability after 48 and 72 hour incubation, compared to the control. Unlike AVM 002, AVM 014 gave rise to 3,4-fold decrease in cell activity at the end of second and third day incubation. Moreover, among all of the tested compounds, AVM 010 was the most toxic at 500.M and 1000.M compared to the control. Furthermore, all the compounds did not show any mutagenic effect on Salmonella typhimurium TA 100 and TA 102 strains.In summary, the results indicate that AVM 002 and AVM 014 is the best candidate to be improved in order to reach higher RT enzyme inhibitory effect and decreased cytotoxicity profile by slight modifications in compound structure.