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

- Competitive Cu2 + binding by curcumin was studied in the presence of two segments of Aβ protein.
- Absorbance and fluorescence spectroscopy of mixed solutions monitored binary and ternary complex formation.
- Mass spectrometry isolated ternary peptide-Cu2 +-curcumin complexes.
- Results showed that curcumin can simultaneously bind to Cu2 + and the Aβ peptide.

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 Cu2 +, known to accelerate amyloid aggregation, and/or curcumin-binding directly to the Aβ protein. To investigate these different roles, curcumin complexation to Cu2 + 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 Cu2 + to some extent in the presence of both segments despite strong peptide-ion interactions. Estimated Cu2 +-curcumin binding affinities in the absence (1.6 × 105 M− 1) and presence (7.9 × 104 M− 1) of the peptide provide quantitative support for this Cu2 + chelation role. With the Aβ14-23 segment, the curcumin simultaneously binds to Cu2 + and the peptide, demonstrating that it can play multiple roles in the prevention of amyloid formation. The stabilities of ternary peptide-Cu2 +-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.