Complexation between Cu(II) and curcumin in the presence of two different segments of amyloid β.

Abstract The natural product curcumin has been shown to play a role in preventing Aβ amyloid fibril formation. This role could include chelation of transition metal ions such as Cu 2 + , known to accelerate amyloid aggregation, and/or curcumin-binding directly to the Aβ protein. To investigate these different roles, curcumin complexation to Cu 2 + was investigated in the presence and absence of two different segments of the Aβ protein including the copper-binding (Aβ6–14) and curcumin-binding (Aβ14–23) domains. Absorbance and fluorescence spectroscopy in 90% water/10% methanol solutions showed that curcumin can bind Cu 2 + to some extent in the presence of both segments despite strong peptide–ion interactions. Estimated Cu 2 + –curcumin binding affinities in the absence (1.6 × 10 5  M − 1 ) and presence (7.9 × 10 4  M − 1 ) of the peptide provide quantitative support for this Cu 2 + chelation role. With the Aβ14–23 segment, the curcumin simultaneously binds to Cu 2 + and the peptide, demonstrating that it can play multiple roles in the prevention of amyloid formation. The stabilities of ternary peptide–Cu 2 + –curcumin complexes were evaluated using ESI mass spectrometry and support the conclusion that curcumin can act as a weak metal ion chelator and also bind directly to the Aβ14–23 peptide segment.