Poster abstracts

Poster number 5 submitted by Grace Cooper

Ligand polarizability modulates tau fibril binding site density

Grace L. Cooper (Dept of Molecular & Cellular Biochemistry, OSU College of Medicine, Chemistry Biology Interface Training Program), Katryna Cisek (Dept of Molecular & Cellular Biochemistry, OSU College of Medicine), Jordan R. Jensen (Dept of Molecular & Cellular Biochemistry, OSU College of Medicine), Kelsey N. Schafer (Dept of Molecular & Cellular Biochemistry, OSU College of Medicine)

Abstract:
Whole brain imaging of tau-bearing neurofibrillary lesions has the potential to improve the premortem diagnosis and staging of Alzheimer’s disease. The discovery of compounds capable of binding synthetic tau aggregates with high affinity suggests that the approach is feasible. However, the utility of candidate radiotracers depends on binding site density (Bmax) as well as affinity, and the drivers of this aspect of ligand-aggregate interaction are unknown. To identify structural features associated with a high-Bmax mode of interaction, the ability of candidate ligands to bind tau filaments was investigated in displacement format. Results showed that displacement efficacy correlated with compound polarizability estimated by quantum property calculations. Within neutral benzothiazole derivatives, polarizability and associated displacement efficacy was increased by maximizing their push-pull character. These data suggest that high polarizability can be fostered in neutral ligands, and that doing so may yield agents with superior diagnostic performance.

Keywords: Alzheimers Disease, Ligand-protein interactions, Computational Chemistry