Biopolym. Cell. 2013; 29(6):473-479.
Structure and Function of Biopolymers
Towards the anti-fibrillogenic activity of phthalocyanines with out-of-plane ligands: correlation with self-association proneness
1Kovalska V. B., 1Losytskyy M. Yu., 1Chernii S. V., 2Chernii V. Ya., 2Tretyakova I. M., 1Yarmoluk S. M., 2Volkov S. V.
  1. Institute of Molecular Biology and Genetics, NAS of Ukraine
    150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03680
  2. Vernadsky Institute of general and inorganic chemistry, NAS of Ukraine
    32/34, prospekt Akademika Palladina, Kyiv, Ukraine, 03142


Aim. The activity of five hafnium phthalocyanines containing out-of-plane ligands as inhibitors of reaction of insulin fibril formation is studied and correlation between their inhibitory properties and tendency to self-association is discussed. Methods. Fluorescence and absorption spectroscopy. Results. For the complexes with weak proneness to self-association PcHfDbm2, PcHfPyr2, and PcHfBtfa2 the values of inhibitory activity were estimated as 60–73 %. For phthalocyanines with the pronounced tendency to self-association PcHfPiromelit and PcHfCl2 the noticeably higher inhibitory activity values (about 95 %) were shown. In the presence of native or fibrilar insulin the destruction of self-associates of metal complex occurs in buffer pH 7.9, Besides upon the conditions of insulin fibrillization reaction (0.1 M HCl) phthalocyanines exist predominantly as monomers. Conclusions. The phthalocyanines with out-of-plane ligands with higher tendency to self-association have shown higher inhibitory activity in the insulin fibril formation comparing with the poorly aggregated metal complexes. At the same time low-order self-associates are not involved directly in the mechanism of inhibition of insulin fibrillization and the phthalocyanines bind with protein in monomeric form. Tendency of phthalocyanines to self-association in aqueous media seems to be an «indicator» of their proneness to stack with protein aromatic amino-acids and thus of anti-fibrilogenic properties.
Keywords: amyloid fibril, phthalocyanines, inhibitors of fibril formation, insulin, aggregation of phthalocyanines, fluorescent dye


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