Role of the carboxy groups of triterpenoids in their inhibition of the nucleation of amyloid β42 required for forming toxic oligomers

Chemical Communications : Chem Comm
Kazuma MurakamiKazuhiro Irie

Abstract

Herein we report that a preferable inhibition of the nucleation phase of Aβ42, related to the formation of toxic oligomers, by triterpenoids from medicinal herbs originates from a salt bridge of their carboxy groups with Lys16 and 28 in Aβ42. Such a direct interaction targeting the monomer, dimer, and trimer suppressed further oligomerization. In contrast, the corresponding congeners without carboxy groups failed to do so.

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Citations

Jun 15, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Kazuma Murakami, Kazuhiro Irie
Sep 21, 2019·Bioscience, Biotechnology, and Biochemistry·Kazuhiro Irie
Nov 1, 2020·International Journal of Biological Macromolecules·Jufei XuWeihong Du
Oct 14, 2019·Journal of Pharmaceutical and Biomedical Analysis·Angela De SimoneVincenza Andrisano
Feb 7, 2021·European Journal of Medicinal Chemistry·Daniela MalafaiaArtur M S Silva
May 10, 2021·International Journal of Biological Macromolecules·Jufei XuWeihong Du
Jun 22, 2021·Bioorganic & Medicinal Chemistry·Helmut M HügelAnthony Lingham
Jan 22, 2022·Journal of Natural Products·Yohei MorishitaTeigo Asai

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Methods Mentioned

BETA
circular dichroism
NMR

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