Studies of anti-fibrillogenic activity of phthalocyanines of zirconium containing out-of-plane ligands

Kovalska, Vladyslava; Losytskyy, Mykhaylo Yu.; Chernii, Viktor; Volkova, Kateryna D.; Tretyakova, Iryna; Черепанов, В. М.; Yarmoluk, S. M.; Волков, С. В.

doi:10.1016/j.bmc.2011.10.083

Cited by 20 publications

(20 citation statements)

References 21 publications

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“…Previously, we have reported the ability of phthalocyanines with out-of-plane ligands to redirect the insulin fibrillization toward the formation of different kinds of aggregates (oligomeric or amorphous species) or cause changes of morphology of fibrils. 7,8 In the presence of earlier studied Hf phthalocyanine bearing quinolinium styryl ligand, the thinning and elongation of the fibrils are observed. 16 Influence of the studied there macrocyclic compounds on the morphology of the formed insulin aggregates is less significant.…”

Section: Scanning Electron Microscopy Studymentioning

confidence: 99%

“…Previously, we have discovered the anti‐fibrillogenic activity of axially coordinated phthalocyanines (Figure S3 in Supporting Information) that are the complexes with “spatial geometry” of the molecule 7, 8, 9. It has been shown that these phthalocyanine complexes are able to affect amyloid aggregation of proteins redirecting their fibrillization toward the formation of oligomeric aggregates or substantially inhibiting the formation of the fibrils 7, 8.…”

Section: Introductionmentioning

confidence: 99%

“…5 According to this study, the inhibitory activity noticeably depends on Previously, we have discovered the anti-fibrillogenic activity of axially coordinated phthalocyanines ( Figure S3 in Supporting Information) that are the complexes with "spatial geometry" of the molecule. [7][8][9] It has been shown that these phthalocyanine complexes are able to affect amyloid aggregation of proteins redirecting their fibrillization toward the formation of oligomeric aggregates or substantially inhibiting the formation of the fibrils. 7,8 The impact of such phthalocyanine on morphology of the formed amyloid aggregates largely depends on the nature of the out-of-plane ligand.…”

Section: Introductionmentioning

confidence: 99%

“…[7][8][9] It has been shown that these phthalocyanine complexes are able to affect amyloid aggregation of proteins redirecting their fibrillization toward the formation of oligomeric aggregates or substantially inhibiting the formation of the fibrils. 7,8 The impact of such phthalocyanine on morphology of the formed amyloid aggregates largely depends on the nature of the out-of-plane ligand.…”

Section: Introductionmentioning

confidence: 99%

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Activity of Zn and Mg phthalocyanines and porphyrazines in amyloid aggregation of insulin

Kovalska

Chernii

Losytskyy

et al. 2017

J of Molecular Recognition

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Formation of the deposits of protein aggregates—amyloid fibrils in an intracellular and intercellular space—is common to a large group of amyloid‐associated disorders. Among the approaches to develop of therapy of such disorders is the use of agents preventing protein fibrillization. Polyaromatic complexes—porphyrins and phthalocyanines—are known as compounds possessing anti‐fibrillogenic activity.Here, we explore the impact of related macrocyclic complexes—phthalocyanines (Pc) and octaphenyl porphyrazines (Pz) of Mg and Zn—on aggregation of amyloidogenic protein insulin. Pz complexes are firstly reported as compounds able to affect protein fibrillization.The effect of Pc and Pz complexes on the kinetics and intensity of insulin aggregation was studied by the fluorescent assay using amyloid sensitive cyanine dye. This has shown the impact of metal ion on the anti‐fibrillogenic properties of macrocyclic complexes—the effect on the fibrillization kinetics of Mg‐containing compounds is much more pronounced comparing to that of Zn analogues.Scanning electron microscopy experiments have demonstrated that filamentous fibrils are the main product of aggregation both for free insulin and in the presence of macrocyclic complexes. However, those fibrils are distinct by their length and proneness to lateral aggregation. The Pc complexes cause the increase in variation of fibrils length 0.9 to 2.7 nm in opposite to 1.4 to 2.0 nm for free insulin, whereas Pz complexes cause certain shortening of the fibrils to 0.8 to 1.6 nm.The averaged size of the fibrils population was estimated by dynamic light scattering; it correlates with the size of single fibrils detected by scanning electron microscopy.

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Section: Scanning Electron Microscopy Studymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Activity of Zn and Mg phthalocyanines and porphyrazines in amyloid aggregation of insulin

Kovalska

Chernii

Losytskyy

et al. 2017

J of Molecular Recognition

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“…Thus, in order to obtain an efficient response to the presence of amyloid fibril, the molecule should have shape complimentary to that of the fibril groove and the size fitting the fibril groove (about 6,5-7 Å) [12]. [11] and AFM image of the insulin amyloid fibrils (right) [13].…”

Section: Introductionmentioning

confidence: 99%

β-ketoenole dyes: Synthesis and study as fluorescent sensors for protein amyloid aggregates

et al. 2016

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The series of the new β-ketoenole dyes ((2E,5Z,7E,9E)-6-hydroxy-2-(alkylamino)-10-phenyldeca-2,5,7,9-tetraen-4-ones) with variation of alkylamino tail groups was synthesized and studied as potential probes for the sensing of protein aggregates amyloid fibrils. The dyes are low fluorescent when free but able to increase their emission intensity in dozens of times in the presence of fibrillar insulin. The fluorescent response of the dye on fibrillar insulin strongly depends on the nature of the alkylamino tail group. For compounds with propylamino (dye 13) and 2-hydroxyethylamino (dye 14) fragments the fluorescence intensity in the presence of fibrillar insulin exceeds that for the native one in 22 and 66 times correspondingly. However dyes demonstrate from low or moderate exceed of the fluorescence intensity in the presence of aggregated lysozyme compared to native one (up to 8.7 times for the dye 53 bearing methyl ester tail group), due to their pronounced sensitivity to native lysozyme. The dyes in complexes with insulin have rather height quantum yield up to 0.15, the large Stokes shifts values (about 100 nm and more), their binding constant values are about 10 5 M -1 . The dye 14 allows fluorescent detection of the insulin amyloid fibrils in the concentration range 1-50 μg/ml. This causes an interest in the future study of the β-ketoenole as prospective fluorescent amyloid-sensitive molecules.

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The impact of binding of macrocyclic metal complexes on amyloid fibrillization of insulin and lysozyme

Kovalska

Chernii

Черепанов

et al. 2017

J of Molecular Recognition

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Amyloid fibrils are insoluble protein aggregates whose accumulation in cells and tissues is connected with a range of pathological diseases. We studied the impact of 2 metal complexes (axially coordinated Hf phthalocyanine and iron (II) clathrochelate) on aggregation of insulin and lysozyme. For both proteins, the host-guest interaction with these compounds changes the kinetics of fibrillization and affects the morphology of final aggregates. The Hf phthalocyanine is a very efficient inhibitor of insulin fibrillization; in its presence, only very low amounts of fibrils with the diameters of 0.8 to 5 nm and spherical aggregates were found. Effective concentration of fibrillization inhibition (IC ) was estimated to be 0.11 ± 0.04 μM. The clathrochelate induced the formation of thin fibrils with the diameters of 0.8 to 2.5 nm; IC was estimated as 20 ± 9 μM. The lysozyme fibrillization remained quite intensive in the presence of the studied compounds; they induced the formation of long filaments (the length up to 2.5 μm, the diameters of 1.5-3.5 nm). These fibrils noticeably differed from those of free lysozyme short linear species (the diameters of 3-5 nm, the length up to 0.6 μm). Thinning and elongation of fibrils suggest that the metal complexes bind mainly to the grooves of protofilaments; this hinders the stacking of early aggregates or protofilaments together but does not hinder their growth. The image of the fibril separated into 2 protofilaments allows suggesting that the fibril formation occurs via the growth of the parallel protofilaments with their subsequent twisting in the fibril. The changes of the lysozyme intrinsic fluorescence indicate that both metal complexes interact with the protein during the stage of the fibrillar seeds formation.

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Studies of anti-fibrillogenic activity of phthalocyanines of zirconium containing out-of-plane ligands

Cited by 20 publications

References 21 publications

Activity of Zn and Mg phthalocyanines and porphyrazines in amyloid aggregation of insulin

Activity of Zn and Mg phthalocyanines and porphyrazines in amyloid aggregation of insulin

β-ketoenole dyes: Synthesis and study as fluorescent sensors for protein amyloid aggregates

The impact of binding of macrocyclic metal complexes on amyloid fibrillization of insulin and lysozyme

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