碩士 / 國立臺灣大學 / 化學研究所 / 106 / Alzheimer''s disease (AD) is a progressive neurodegenerative disease, in which dementia symptoms gradually worsen over a number of years. AD usually begins in people over 65 years of age.The cause of most Alzheimer''s cases is still not confirmed. Several competitive hypotheses exist trying to explain the account of the disease. My research topic is on the basis of amyloid hypothesis.First of all, thioflavin-T is a benzothiazole salt used for histology staining and biophysical studies in visualizing and quantifying the presence of misfolded protein aggregates such as amyloid. On the other hand, lenalidomide is an immunomodulatory drug, which has been identified to interact with the ubiquitin E3 ligase. Targeting this enzyme will cause the degradation of Ikaros transcription factors IKZF1 and IKZF3.
My research aim is to introduce an appropriate linker for conjugation of the above-mentioned critical compounds. Since thioflavin-T is an amyloid binder, and lenalidomide is a known ubiquitin binder, the conjugated product may initiate ubiquitination to degrade amyloid protein. In this way, the conjugate compound incorporating an appropriate linker can attain the desired lipophilicity without severe steric hindrance to binding amyloid and ubiquitin E3 ligase. In this study, we have synthesized the first thioflavin−lenalidomide conjugate compound, which will be subject to bioactivity tests.
| Identifer | oai:union.ndltd.org:TW/106NTU05065064 |
| Date | January 2018 |
| Creators | Bo-Ruei Chen, 陳博睿 |
| Contributors | 方俊民 |
| Source Sets | National Digital Library of Theses and Dissertations in Taiwan |
| Language | zh-TW |
| Detected Language | English |
| Type | 學位論文 ; thesis |
| Format | 187 |
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