1,5-Diazacyclooctanes, as Exclusive Oxidative Polyamine Metabolites, Inhibit Amyloid- β(1-40) Fibrillization

Ayumi Tsutsui; Tamotsu Zako; Tong Bu; Yoshiki Yamaguchi; Mizuo Maeda; Katsunori Tanaka

doi:10.1002/advs.201600082

1,5-Diazacyclooctanes, as Exclusive Oxidative Polyamine Metabolites, Inhibit Amyloid- β(1-40) Fibrillization

Adv Sci (Weinh). 2016 Jun 1;3(10):1600082. doi: 10.1002/advs.201600082. eCollection 2016 Oct.

Authors

Ayumi Tsutsui¹, Tamotsu Zako², Tong Bu², Yoshiki Yamaguchi³, Mizuo Maeda², Katsunori Tanaka⁴

Affiliations

¹ Biofunctional Synthetic Chemistry Laboratory RIKEN Hirosawa, Wako-shi Saitama 351-0198 Japan.
² Bioengineering Laboratory RIKEN Hirosawa, Wako-shi Saitama 351-0198 Japan.
³ Systems Glycobiology Research Group RIKEN-Max Plank Joint Research Center for Systems Chemical Biology RIKEN Global Research Cluster RIKEN Hirosawa, Wako-shi Saitama 351-0198 Japan.
⁴ Biofunctional Synthetic Chemistry Laboratory RIKEN Hirosawa, Wako-shi Saitama 351-0198 Japan; Biofunctional Chemistry Laboratory A. Butlerov Institute of Chemistry Kazan Federal University 18 Kremlyovskaya Street Kazan 420008 Russia; JST-PRESTO Hirosawa, Wako-shi Saitama 351-0198 Japan.

Abstract

Biologically relevant 1,5-diazacyclooctanes derived from polyamines and acrolein, inhibit Aβ40 peptide fibrillization and significantly suppress cell cytotoxicity. Formal [4+4] cycloaddition reaction of imines is thus involved in modulating oxidative stress processes associated with neural diseases.

Keywords: acrolein; amyloid; cycloaddition; oxidative stress; polyamine.