title: Anti-fibrillogenic properties of phthalocyanines: effect of the out-of-plane ligands.
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 2-8nm 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.
authors.affiliation: Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, Zabolotnogo st. 150, 03143 Kyiv, Ukraine. Electronic address: v.kovalska@gmail.com.
authors.forename: V
authors.initials: V
authors.lastname: Kovalska
authors.affiliation: Institute of Physics, National Academy of Sciences of Ukraine, Nauky ave. 46, 03680 Kyiv, Ukraine.
authors.forename: V
authors.initials: V
authors.lastname: Cherepanov
authors.affiliation: Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, Zabolotnogo st. 150, 03143 Kyiv, Ukraine.
authors.forename: M
authors.initials: M
authors.lastname: Losytskyy
authors.affiliation: Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, Zabolotnogo st. 150, 03143 Kyiv, Ukraine.
authors.forename: S
authors.initials: S
authors.lastname: Chernii
authors.affiliation: Institute of Physics, National Academy of Sciences of Ukraine, Nauky ave. 46, 03680 Kyiv, Ukraine.
authors.forename: A
authors.initials: A
authors.lastname: Senenko
authors.affiliation: Institute of General and Inorganic Chemistry, National Academy of Sciences of Ukraine, Palladin ave. 32/34, 03680 Kyiv, Ukraine.
authors.forename: V
authors.initials: V
authors.lastname: Chernii
authors.affiliation: Institute of General and Inorganic Chemistry, National Academy of Sciences of Ukraine, Palladin ave. 32/34, 03680 Kyiv, Ukraine.
authors.forename: I
authors.initials: I
authors.lastname: Tretyakova
authors.affiliation: Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, Zabolotnogo st. 150, 03143 Kyiv, Ukraine.
authors.forename: S
authors.initials: S
authors.lastname: Yarmoluk
authors.affiliation: Institute of General and Inorganic Chemistry, National Academy of Sciences of Ukraine, Palladin ave. 32/34, 03680 Kyiv, Ukraine.
authors.forename: S
authors.initials: S
authors.lastname: Volkov
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D007211:Indoles / Q000737:chemistry* / Q000378:metabolism; D007328:Insulin / Q000737:chemistry / Q000378:metabolism; D054833:Isoindoles; D007700:Kinetics; D008024:Ligands; D018625:Microscopy, Atomic Force; D008969:Molecular Sequence Data
chemical_list: D007211:Indoles; D007328:Insulin; D054833:Isoindoles; D008024:Ligands; C013647:phthalocyanine
keywords: Amyloid fibril; Anti-fibrillogenic activity; Atomic force microscopy; Fluorescent assay; Insulin; Phthalocyanines; Protein aggregation