Jun-Liang Yao

A comparative study of the interaction of two structurally analogous ruthenium complexes with human telomeric G-quadruplex DNA

Two new polypyridine ligands and their corresponding ruthenium(II) complexes have been prepared and characterized. The interactions of both complexes with human telomere quadruplex DNA (both the antiparallel basket and the mixed-hybrid G-quadruplex) have been studied by circular dichroism (CD), CD melting, UV-visible (UV-Vis), fluorescent intercalator displacement (FID) assays and molecular docking studies. The results show that both complexes can stabilize G-quadruplexes DNA and two complexes show different binding affinity for different G-quadruplexes DNA. The 1:1 stoichiometry was confirmed in the buffered solutions by the UV-Vis spectrophotometer using Jobs plot method and molecular docking studies. We have also investigated the interaction between the complexes and duplex DNA to gain some insight into the selectivity of the complexes for G-quadruplex structures. FID studies have shown that the complexes have a modest selectivity for G-quadruplex versus duplex DNA.

Molecular Hairpin: A Possible Model for Inhibition of Tau Aggregation by Tannic Acid

Inhibition of anomalous aggregation of tau protein would be an attractive therapeutic target for Alzheimers disease (AD). In this study, tannic acid (TA), a polymeric plant polyphenol, and its monomer, gallic acid (GA), were introduced as the references to afford a molecular framework that integrates tau binding properties and inhibitory effects. Using a thioflavin S fluorescence assay and electron microscopy, we demonstrated that TA could competently inhibit the in vitro aggregation of tau peptide R3, corresponding to the third repeat unit of the microtubule-binding domain, with an IC50 of 3.5 μM, while GAs inhibition was comparatively piddling (with an IC50 of 92 μM). In the isothermal titration calorimetry experiment, we found that TA could strongly bind to R3 with a large amount of heat released. Circular dichroism spectra showed TA dose-dependently suppressed the conformational transition of R3 from a random coil structure to a β-sheet structure during the aggregation process. Finally, a structural model was built using molecular docking simulation to elucidate the possible binding sites for TA on the tau peptide surface. Our results suggest that TA recognizably interacts with tau peptide by forming a hairpin binding motif, a key framework required for inhibiting tau polymerization, in addition to hydrogen bonding, hydrophilic-hydrophobic interactions, and static electrical interactions, as reported previously. The inhibitory effect of TA on human full-length tau protein (tau441) was also verified by electron microscopy. This finding hints at the possibility of TA as a leading compound of anti-AD drugs and offers a new stratagem for the rational molecular design of a tau aggregation inhibitor.