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Rational Design of a Cocktail of Inhibitors against Aβ Aggregation |
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| Authors: | Dr Gao Li Wu-Yue Yang Wen-Hao Li Yun-Yi Luo Yeh-Jun Lim Prof?Dr Yang Li Dr Ashim Paul Prof?Dr Daniel Segal Liu Hong Prof?Dr Yan-Mei Li |
| Institution: | 1. Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, 100084 Beijing, P. R. China;2. Zhou Pei-Yuan Center for Applied Mathematics, Tsinghua University, 100084 Beijing, P. R. China
These authors contributed equally to this work.;3. Institute for Science and Technology, Shandong University of, Traditional Chinese Medicine, 250355 Jinan, P. R. China;4. School of Molecular Microbiology & Biotechnology, Tel Aviv University, 69978 Tel Aviv, Israel;5. School of Molecular Microbiology & Biotechnology, Tel Aviv University, 69978 Tel Aviv, Israel Sagol Interdisciplinary School of Neurosciences, Tel Aviv University, 69978 Tel Aviv, Israel;6. Zhou Pei-Yuan Center for Applied Mathematics, Tsinghua University, 100084 Beijing, P. R. China |
| Abstract: | It has been reported that many molecules could inhibit the aggregation of Aβ (amyloid-β) through suppressing either primary nucleation, secondary nucleation, or elongation processes. In order to suppress multiple pathways of Aβ aggregation, we screened 23 small molecules and found two types of inhibitors with different inhibiting mechanisms based on chemical kinetics analysis. Trp-glucose conjugates ( AS2 ) could bind with fibril ends while natural products ( D3 and D4 ) could associate with monomers. A cocktail of these two kinds of molecules achieved co-inhibition of various fibrillar species and avoid unwanted interference. |
| Keywords: | amyloid beta-peptides chemical kinetics analysis cocktail inhibitor |