Anti-fibrillogenic properties of phthalocyanines: Effect of the out-of-plane ligands

• Published in: Bioorganic & medicinal chemistry 2014-12, Vol.22 (24), p.6918-6923
• Main Authors: Kovalska, V., Cherepanov, V., Losytskyy, M., Chernii, S., Senenko, A., Chernii, V., Tretyakova, I., Yarmoluk, S., Volkov, S.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Amyloid fibril; Animals; Anti-fibrillogenic activity; Atomic force microscopy; Cattle; Fluorescent assay; Indoles - chemistry; Indoles - metabolism; Insulin; Insulin - chemistry; Insulin - metabolism; Kinetics; Ligands; Microscopy, Atomic Force; Molecular Sequence Data; Phthalocyanines; Protein aggregation
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2014.10.024

[Display omitted] The axially-coordinated phthalocyanines were previously reported as agents possessing strong anti-fibrillogenic properties. In the presented study we used the atomic force microscopy to investigate the intermediates and the products of insulin aggregation reaction formed in the presence of Zr and Hf phthalocyanine complexes that contain out-of-plane ligands of different size and nature. It is shown that while phthalocyanine-free insulin generated mostly amyloid fibrils with a diameter of 2–8nm and a length of up to 5μm, the presence of phthalocyanines with spatial bulky ligands (PcZrDbm2) leads to the redirection of the fibrillization reaction to the formation of the spherical oligomer aggregates with a diameter of 4–12nm. At the same time the phthalocyanine complex PcHfCl2 having the small-volume ligands induces the formation of large size insulin aggregates with a height of about 100nm that are supposed to be amorphous species. The study of the aggregation intermediates showed the certain similarity of the reaction passing for phthalocyanine-free insulin and insulin in the presence of PcZrDbm2. The large-size amorphous species were observed at the beginning of reaction, later they dissociated, leading to the formation and growth of the smaller size particles. The amyloid-sensitive cyanine dye 7519 demonstrates the strong fluorescent response both in the presence of fibrils and spherical oligomers, while it is non-sensitive to amorphous aggregates.