文摘
In this article, we first designed and synthesized curcumin-based near-infrared (NIR) fluorescence imaging probes for detecting both soluble and insoluble amyloid beta (A尾) species and then an inhibitor that could attenuate cross-linking of A尾 induced by copper. According to our previous results and the possible structural stereohindrance compatibility of the A尾 peptide and the hydrophobic/hydrophilic property of the A尾13鈥?0 (HHQKLVFF) fragment, NIR imaging probe CRANAD-58 was designed and synthesized. As expected CRANAD-58 showed significant fluorescence property changes upon mixing with both soluble and insoluble A尾 species in vitro. In vivo NIR imaging revealed that CRANAD-58 was capable of differentiating transgenic and wild-type mice as young as 4 months old, the age that lacks apparently visible A尾 plaques and A尾 is likely in its soluble forms. According to our limited studies on the interaction mechanism between CRANAD-58 and A尾, we also designed CRANAD-17 to attenuate the cross-linking of A尾42 induced by copper. It is well-known that the coordination of copper with imidazoles on Histidine-13 and 14 (H13, H14) of A尾 peptides could initialize covalent cross-linking of A尾. In CRANAD-17, a curcumin scaffold was used as an anchoring moiety to usher the designed compound to the vicinity of H13 and H14 of A尾, and imidazole rings were incorporated to compete with H13/H14 for copper binding. The results of SDS-PAGE gel and Western blot indicated that CRANAD-17 was capable of inhibiting A尾42 cross-linking induced by copper. This raises a potential for CRANAD-17 to be considered for AD therapy.