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.
- Institute of Molecular Biology and Genetics, NAS of Ukraine
150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03680 - Vernadsky Institute of General and Inorganic Chemistry, NAS of Ukraine
32/34, prospekt Akademika Palladina, Kyiv, Ukraine, 03142
Abstract
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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