Identification of a Putative α-synuclein Radioligand Using an in silico Similarity Search.

ABSTRACT:

Purpose

Previous studies from our lab utilized an ultra-high throughput screening method to identify compound 1 as a small molecule that binds to alpha-synuclein (α-synuclein) fibrils. The goal of the current study was to conduct a similarity search of 1 to identify structural analogs having improved in vitro binding properties for this target that could be labeled with radionuclides for both in vitro and in vivo studies for measuring α-synuclein aggregates.

Methods

Using 1 as a lead compound in a similarity search, isoxazole derivative 15 was identified to bind to α-synuclein fibrils with high affinity in competition binding assays. A photocrosslinkable version was used to confirm binding site preference. Derivative 21, the iodo-analog of 15, was synthesized, and subsequent

SUBMITTER: Janssen B 

PROVIDER: S-EPMC10527666 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature