Format

Send to

Choose Destination
ACS Chem Neurosci. 2019 Jan 16;10(1):573-587. doi: 10.1021/acschemneuro.8b00436. Epub 2018 Oct 19.

Conformational-Switch Based Strategy Triggered by [18] π Heteroannulenes toward Reduction of Alpha Synuclein Oligomer Toxicity.

Author information

1
Structural Biology and Bioinformatics Division , CSIR-Indian Institute of Chemical Biology , 4 Raja S. C. Mullick Road , Kolkata 700032 , India.
2
School of Chemical Sciences , Indian Association for the Cultivation of Science (IACS) , 2A/2B Raja S. C. Mullick Road , Kolkata 700032 , India.

Abstract

A water-soluble meso-carboxy aryl substituted [18] heteroannulene (porphyrin) and its Zn-complex have been found to be viable in targeting α-Syn aggregation at all its key microevents, namely, primary nucleation, fibril elongation, and secondary nucleation, by converting the highly heterogeneous and cytotoxic aggresome into a homogeneous population of minimally toxic off-pathway oligomers, that remained unexplored until recently. With the EC50 and dissociation constants in the low micromolar range, these heteroannulenes induce a switch in the secondary structure of toxic prefibrillar on-pathway oligomers of α-Syn, converting them into minimally toxic nonseeding off-pathway oligomers. The inhibition of the aggregation and the reduction of toxicity have been studied in vitro as well as inside neuroblastoma cells.

KEYWORDS:

Heteroannulenes; conformational switch; neuroblastoma cell; off-pathway oligomer; on-pathway oligomer; α-Syn

Supplemental Content

Full text links

Icon for American Chemical Society
Loading ...
Support Center