Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, 150 Zabolotnogo St., 03143 Kyiv, Ukraine.
Bioorg Med Chem. 2012 Jan 1;20(1):330-4. doi: 10.1016/j.bmc.2011.10.083. Epub 2011 Nov 6.
Series of phthalocyanines of zirconium containing lysine, citric, nonanoic acid residues and dibenzolylmethane groups as out-of-plane ligands are firstly studied as inhibitors of fibrillogenesis using cyanine-based fluorescent inhibitory assay. It was shown that studied phthalocyanines at concentration of 20μM inhibited aggregation reaction on 38.5-57.6% and inhibitory activity of phthalocyanines depended on the chemical nature of out-of-plane ligand. For the most active compound PcZrLys(2) (zirconium phthalocyanine containing lysine fragment) the efficient inhibitor concentration was estimated to be 37μM. AFM studies have shown that in the presence of PcZrLys(2) the inhibition of fibrils formation and formation of spherical oligomeric aggregates took place. Due to the ability of phthalocyanines to decrease efficiently protein aggregation into the amyloid fibrils, modification of phthalocyanine molecules via out-of-plane substitutions was proposed as approach for design of anti-fibrillogenic agents with required properties.
首次研究了一系列含有赖氨酸、柠檬酸、壬酸残基和二苯甲酮基团作为平面外配体的锆酞菁，作为基于花青的荧光抑制测定法的纤维形成抑制剂。结果表明，研究的酞菁在 20μM 的浓度下抑制了 38.5-57.6%的聚集反应，并且酞菁的抑制活性取决于平面外配体的化学性质。对于最活跃的化合物 PcZrLys(2)（含有赖氨酸片段的锆酞菁），有效抑制剂浓度估计为 37μM。原子力显微镜研究表明，在 PcZrLys(2) 的存在下，抑制了纤维的形成和球形寡聚体聚集物的形成。由于酞菁能够有效地将蛋白质聚集物减少到淀粉样纤维中，因此通过平面外取代来修饰酞菁分子被提议作为设计具有所需性质的抗纤维形成剂的方法。
