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To identify small molecules binding non-covalently to soluble proteins or protein aggregates


We developed a gel permeation LC-MS based assay to measure direct binding of small molecules to protein aggregates or to soluble proteins. The advantage of our binding assay compared to traditional radioligand binding assays is that it does not require radiolabeled material. It was used to support a tracer discovery project for the development of novel radioligands for positron emission tomography (PET) imaging in human brain specific to protein aggregates. Direct binders were selected by screening a 1000 compounds library and their specificity of interaction to aggregates was evaluated testing their ability of binding to a pool of proteins from a brain homogenate extract.