Synthesis and Characterization of Thiophene-based Donor-Acceptor-Donor Heptameric Ligands for Spectral Assignment of Polymorphic Amyloid-beta Deposits

Protein deposits are associated with many devastating diseases and fluorescent ligands able to visualize these pathological entities are essential. Here, we report the synthesis of thiophene-based donor-acceptor-donor heptameric ligands that can be utilized for spectral assignment of distinct amyloid-beta (A beta) aggregates, one of the pathological hallmarks in Alzheimers disease. The ability of the ligands to selectively distinguish A beta deposits was abolished when the chemical composition of the ligands was altered. Our findings provide the structural and functional basis for the development of new fluorescent ligands that can distinguish between aggregated proteinaceous species consisting of the same peptide or protein. In addition, such ligands might aid in interpreting the potential role of polymorphic A beta deposits in the pathogenesis of Alzheimers disease.
Funding Agencies|Swedish Research CouncilSwedish Research Council [2016-00748]; Erling Persson foundation