Anti-oligomerization sheet molecules: Design, synthesis and evaluation of inhibitory activities against α-synuclein aggregation. Issue 14 (15th July 2019)

• Record Type: Journal Article
• Authors: Liu, Hao; Chen, Li; Zhou, Fei; Zhang, Yun-Xiao; Xu, Ji; Xu, Meng; Bai, Su-Ping
• Is Part Of: Bioorganic & medicinal chemistry. Volume 27:Issue 14(2019)
• Page Start: 3089
• Page End: 3096
• Publication Date: 2019-07-15
• Subjects: α-Synuclein -- Anti-aggregation -- Inhibitor -- Synthesis; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2019.05.032
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: Aggregation of α-synuclein (α-Syn) play a key role in the development of Parkinson Disease (PD). One of the effective approaches is to stabilize the native, monomeric protein with suitable molecule ligands. We have designed and synthesized a series of sheet-like conjugated compounds which possess different skeletons and various heteroatoms in the two blocks located at both ends of linker, which have good π-electron delocalization and high ability of hydrogen-bond formation. They have shown anti-aggregation activities in vitro towards α-Syn with IC50 down to 1.09 μM. The molecule is found binding in parallel to the NACore within NAC domain of α-Syn, interfering aggregation of NAC region within different α-Syn monomer, and further inhibiting or slowing down the formation of α-Syn oligomer nuclei at lag phase. The potential inhibitor obtained by our strategy is considered to be highly efficient to inhibit α-Syn aggregation.