Advanced Electron Paramagnetic Resonance Studies of a Ternary Complex of Copper, Amyloid-β, and a Chemical Regulator

Sugyeong Hong; Yoo Kyung Go; Jeffrey S Derrick; Sanghun Han; Jin Kim; Mi Hee Lim; Sun Hee Kim

doi:10.1021/acs.inorgchem.8b01824

Advanced Electron Paramagnetic Resonance Studies of a Ternary Complex of Copper, Amyloid-β, and a Chemical Regulator

Inorg Chem. 2018 Oct 15;57(20):12665-12670. doi: 10.1021/acs.inorgchem.8b01824. Epub 2018 Sep 21.

Authors

Sugyeong Hong^{1

2}, Yoo Kyung Go¹, Jeffrey S Derrick³, Sanghun Han⁴, Jin Kim¹, Mi Hee Lim⁵, Sun Hee Kim^{1

2}

Affiliations

¹ Western Seoul Center , Korea Basic Science Institute , Seoul 03759 , Republic of Korea.
² Department of Chemistry and Nano Science , Ewha Womans University , Seoul 03760 , Republic of Korea.
³ Department of Chemistry , Ulsan National Institute of Science and Technology , Ulsan 44919 , Republic of Korea.
⁴ Department of Materials Science and Engineering , Seoul National University , Seoul 08826 , Republic of Korea.
⁵ Department of Chemistry , Korea Advanced Institute of Science and Technology , Daejeon 34141 , Republic of Korea.

PMID: 30239184
DOI: 10.1021/acs.inorgchem.8b01824

Abstract

Although there has been extensive effort to develop chemical regulators, progress has been static, in part because of these regulators' unclear mechanisms. Here, we report using advanced electron paramagnetic resonance (EPR) spectroscopy to obtain the first molecular-level structural information regarding a ternary complex of Cu^II-amyloid-β (Aβ) with a chemical regulator that can specifically modulate Cu-induced Aβ aggregation. Our advanced EPR spectroscopic results revealed that a chemical regulator (1) for Cu^II-Aβ_1-16 disrupted the coordination environment of Cu^II in Aβ, resulting in the detachment of the primary amine at the N-terminal and a carbonyl group between Asp1 and Ala2 from the Cu^II center and the subsequent formation of a ternary complex, chemical regulator-Cu^II-Aβ_1-16. Therefore, our results demonstrate how a chemical regulator interacts with metal-Aβ at the molecular level. These findings provide novel insight into working mechanisms and thereby contribute to the establishment of a rational design for chemical regulators of metal-Aβ complexes.