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| Type |
Poster Presentation |
| Area |
Organic Chemistry |
| Room No. |
Event Hall |
| Time |
4월 19일 (목요일) 11:00~12:30 |
| Code |
ORGN.P-445 |
| Subject |
Development of a real-time FRET detection system for amyloid-β plaque formation towards therapeutic treatment of alzheimer disease |
| Authors |
Yeon Gyo Hwang, Sang Jeon Chung1,*
Pharmacy, Sungkyunkwan University, Korea
1Department of Chemistry, SungKyunKwan University, Korea
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| Abstract |
Alzheimer disease (AD) occurs by aggregation of amyloid-β and its accumulation of amyloid-β plaque in the brain can be fatal. Amyloid-β is formed by the cleavage of the amyloid protein precursor (APP). Aggregation of amyloid-β is highly influenced by high concentrations of metal (II) ions in the brain. These metal ions coordinate especially with histidine, glutamic acid, and aspartic acid residues of amyloid-β. There are several methods to detect amyloid-β aggregation, for example, the use of nuclear magnetic resonance (NMR) and transmission electron microscopy (TEM). However, these techniques can be laborious, expensive, and often requires dedicated instruments. To overcome the drawbacks of the aforementioned methods, we designed a fast and reliable system to detect amyloid-β aggregation based on Förster resonance energy transfer (FRET). Real-time imaging of amyloid-β aggregation was achieved using an amyloid-β fragment equipped with an N-terminus unnatural fluorescent amino acid, 1-naphthylamine. In our design, a C-terminal tryptophan residue of the amyloid-β fragment act as the FRET donor to the 1-naphthylamine residue. However, only upon aggregation of the construct, the FRET pair is in close proximity to allow energy transfer. Consequently, excitation at 280 nm (i.e., tryptophan excitation maximum) results in significant sensitized emission at 430 nm (i.e, 1-naphthylamine emission maximum) upon addition of a metal ion to the artificial amyloid-β fragment. Our FRET based approach allows monitoring of the metal ion induced amyloid-β plaque formation. The developed method may be applicable in the high throughput screening of potential inhibitors of amyloid-β aggregation for the therapeutic treatment of AD. |
| E-mail |
dusry411@naver.com |
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121st General Meeting of the KCS