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Anti-fibrillogenic properties of phthalocyanines: Effect of the out-of-plane ligands
Institution:1. Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, Zabolotnogo st. 150, 03143 Kyiv, Ukraine;2. Institute of Physics, National Academy of Sciences of Ukraine, Nauky ave. 46, 03680 Kyiv, Ukraine;3. Institute of General and Inorganic Chemistry, National Academy of Sciences of Ukraine, Palladin ave. 32/34, 03680 Kyiv, Ukraine;1. Key Laboratory of Novel Thin Film Solar Cells, Institute of Plasma Physics, Chinese Academy of Sciences, Hefei 230031, PR China;2. School of Renewable Energy, North China Electric Power University, Beijing 102206, PR China;3. Hefei National Laboratory for Physical Sciences at Microscale, Department of Materials Science and Engineering, University of Science and Technology of China (USTC), Hefei 230026, PR China;1. Department of Materials Science and Technology, Faculty of Engineering, Gifu University, Yanagido, Gifu 501-1193, Japan;2. Research Center of Organic Electronics, Yamagata University, 4-3-16, Jonan, Yonezawa, Yamagata 992-8510, Japan;3. Department of Chemical Engineering, Chonnam National University, Gwangju 500-757, South Korea;4. Chemicrea. Inc., 1-133 Ohtsurugi, Shimogawa, Izumi-machi, Iwaki, Fukushima 971-8183, Japan;1. N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 119991 Moscow, Russia;2. Department of Immunobiology of Bacteria, Institute of Microbiology, Biotechnology and Immunology, University of Lodz, PL 90-237 Lodz, Poland;3. TEDA School of Biological Sciences and Biotechnology, Nankai University, TEDA, 300457 Tianjin, PR China;1. Engineering Faculty, Department of Chemical Engineering, Marmara University, 34722 Göztepe, Istanbul Turkey;2. Faculty of Arts and Sciences, Department of Chemistry, Eskişehir Osmangazi University, 26480, Eskişehir, Turkey;3. Yenice Vocational School, Çanakkale 18 March University, Yenice, Çanakkale, Turkey;4. Department of Chemistry, Yıldız Technical University, 34210 Esenler, Istanbul, Turkey;1. Department of Chemistry, Sakarya University, TR-54187 Esentepe, Sakarya, Turkey;2. Department of Physics, Marmara University, TR-34722 Göztepe, Istanbul, Turkey
Abstract: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 2–8 nm and a length of up to 5 μm, 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 4–12 nm. 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 100 nm 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.
Keywords:Protein aggregation  Amyloid fibril  Anti-fibrillogenic activity  Phthalocyanines  Insulin  Atomic force microscopy  Fluorescent assay
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