| 摘要 |
We have developed a high through-put screen capable of isolating inhibitors of polypeptide aggregation, such as Alzheimer's Disease polypeptide Abeta aggregation, or other disease state aggregating proteins, from amidst large libraries of candidate inhibitors. The screen uses a fusion of a polypeptide domain that self-aggregates, such as an Abeta42 domain characteristic of Alzheimer's disease plaques, to a reporter construct, such as Green Fluorescent Protein (GFP) or similar fluorescent protein. In the absence of inhibition, the rapid misfolding and aggregation of Abeta42 causes the entire fusion protein to misfold, thereby preventing fluorescence. Compounds that inhibit Abeta42 aggregation enable GFP to fold into its native structure, and can be identified by the resulting fluorescent signal.
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