abs

학술발표회초록보기

초록문의 abstract@kcsnet.or.kr

결제문의 member@kcsnet.or.kr

현재 가능한 작업은 아래와 같습니다.
  • 05월 20일 18시 이후 : 초록수정 불가능, 일정확인 및 검색만 가능

제125회 대한화학회 학술발표회 및 총회 Mechanistic approaches for chemically modifying the coordination sphere of copper–amyloid-β complexes

등록일
2020년 1월 28일 11시 23분 43초
접수번호
0068
발표코드
INOR.P-78 이곳을 클릭하시면 발표코드에 대한 설명을 보실 수 있습니다.
발표시간
온라인 PDF 제출
발표형식
포스터
발표분야
Inorganic Chemistry
저자 및
공동저자
Jiyeon Han, Mi Hee Lim*
Department of Chemistry, Korea Advanced Institute of Science and Technology, Korea
Neurotoxic implications of the interactions between Cu(I/II) and amyloid-β (Aβ) indicate a connection between amyloid cascade hypothesis and metal ion hypothesis with respect to the neurodegeneration associated with Alzheimer’s disease (AD). Herein, we report a mechanistic strategy for modifying the first coordination sphere of Cu(II) bound to Aβ utilizing a rationally designed peptide modifier, L1. Upon reacting with L1, a metal-binding histidine (His) residue, His14, in Cu(II)–Aβ was modified through either covalent adduct formation, oxidation, or both. Consequently, the reactivity of L1 with Cu(II)–Aβ was able to disrupt binding of Cu(II) to Aβ and result in chemically modified Aβ with altered aggregation and toxicity profiles. Our molecular-level mechanistic studies revealed that such L1-mediated modifications toward Cu(II)–Aβ could stem from the molecule’s ability to 1) interact with Cu(II)–Aβ and 2) foster copper–O2 chemistry. Collectively, our work demonstrates the development of an effective approach to modify Cu(II)–Aβ at a metal-binding amino acid residue and consequently alter Aβ’s coordination to copper, aggregation, and toxicity, supplemented with an in-depth mechanistic perspective regarding such reactivity.

상단으로