| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1370703 | Bioorganic & Medicinal Chemistry Letters | 2015 | 4 Pages |
Inhibition of amyloid-β (Aβ) aggregation could be a drug development target for treating Alzheimer disease. Insufficient activity to inhibit aggregation, however, remains a key issue. Here, we report a covalent modifier-type aggregation inhibitor of Aβ, diazirine-equipped cyclo-KLVF(β-Ph)F (2). Due to the affinity of the cyclo-KLVFF motif for Aβ, 2 selectively reacted with Aβ1–42 under UV-light irradiation to form an irreversible covalent bond. The Tyr-10 residue of Aβ1–42 was identified as the covalent modification site with 2. The extent of cross-β-sheet structure, characteristics of amyloid aggregation, and toxicity of Aβ1–42 were strongly attenuated by this chemical modification.
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