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PDFOpen Access (License Unspecified), Open Access
Thesis
Development of a small molecule drug for inhibition of TIPE2 protein function
Master of Science (M.S.), Drexel University
Jun 2020
DOI:
https://doi.org/10.17918/00001384
Abstract
This work focuses on designing a small molecule drug to inhibit the function of TNF-[alpha]-induced protein 8-like 2 (TIPE2). The protein is known to play an important role in leukocyte polarization and migration, both of which are exploited by tumor cells in cases of cancer to sustain its proliferation and growth. Several hit compounds were pre-selected based on their TIPE2-binding affinity, and their virtual modification is discussed in this work. Avogadro and PyRx were used to determine the conformation of the ligand and the protein-ligand binding affinity, respectively. Binding interactions between different functional groups and TIPE2 are discussed in detail and provide additional insight to the structure of the TIPE2 binding pocket. The protein has a highly hydrophobic cavity which interacts best with aromatic groups. At the same time, aromatic substituents have been found to decrease solubility of compounds far below the desired limit. Introducing N-containing heterocycles is an efficient modification strategy that has been found to give the most optimal balance between desired properties. Two best compounds were selected due to their highest binding score of -11.1 kcal/mol and their solubility values of greater than -3.0 logS. Synthetic pathway was developed for one of the compounds, with alternative methods available to either improve the efficiency or decrease the cost of the process.
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Details
- Title
- Development of a small molecule drug for inhibition of TIPE2 protein function
- Creators
- Viktoriia Sokolova
- Contributors
- Haifeng Ji (Advisor)
- Awarding Institution
- Drexel University
- Degree Awarded
- Master of Science (M.S.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- iv, 50 pages
- Resource Type
- Thesis
- Language
- English
- Academic Unit
- College of Arts and Sciences; Chemistry; Drexel University
- Other Identifier
- 991014695137504721