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

The natural product curcumin has been shown to play a role in preventing A beta 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 A beta protein. To investigate these different roles, curcumin complexation to Cu2+ was investigated in the presence and absence of two different segments of the A beta protein including the copper-binding (A beta 6-14) and curcumin-binding (A beta 14-23) 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 x 10(5) M-1) and presence (7.9 x 10(4) M-1) of the peptide provide quantitative support for this Cu2+ chelation role. With the A beta 14-23 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 A beta 14-23 peptide segment. (C) 2013 Elsevier B.V. All rights reserved.