| 학회 | 한국고분자학회 |
| 학술대회 | 2005년 봄 (04/14 ~ 04/15, 전경련회관) |
| 권호 | 30권 1호, p.468 |
| 발표분야 | 의료용 고분자 부문위원회 |
| 제목 | Binding Energetics of Synthetic Inhibitors for Alzheimer’s Disease: A molecular analysis for competitive binding with β–secretase |
| 초록 | The pathogenesis of Alzheimer’s disease (AD) is intimately related to the presence of the neurotoxic amyloid-β peptide (Aβ) in the brain.1 A key step in the production of Aβ is the cleavage of a membrane protein called the amyloid precursor protein (APP) by a protease known as β–secretase.2 Tang and co-workers have synthesized competitive inhibitors for the reduction of Aβ by utilizing the template of the β–secretase site of APP.3 Although several potent inhibitors have been reported, it is not clear whether or not these inhibitors are really competitive enough to prevent APP from binding to β–secretase. In the present work, we have calculated binding free energies of APP and inhibitors with β-secretase using the CHARMM program in order to investigate the inhibition activity of those proposed inhibitors. It is revealed from the calculation that the free energy of binding with β–secretase for APP is lower than that for inhibitor, which suggests that those inhibitors may not stop the production of Aβ in vivo. Fig 1. The time evaluation of the free energy of binding with β–secretase for APP and inhibitor Reference 1. Selkoe, D. J. Nature 1999, 399A, A23-A31 2. Robert Vassar, Brain D. Bennett, M. Citron et al. Science 1999, 286, 735-741 3. A. K. Ghosh, J. Tang et al. J. Am. Chem. Soc. 2000, 122, 3522-3523 |
| 저자 | 최진, 최호섭, 허준, 조원호 |
| 소속 | 서울대 |
| 키워드 | Alzheimer’s Disease; β–secretase; Inhibitor |
