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

• Published in: Journal of molecular recognition 2018-01, Vol.31 (1), p.n/a
• Main Authors: Kovalska, V., Chernii, S., Losytskyy, M., Ostapko, J., Tretyakova, I., Gorski, A., Chernii, V., Yarmoluk, S.
• Format: Article
• Language: English
• Subjects: Agglomeration; Amyloid; Amyloid - chemistry; Amyloid - ultrastructure; amyloid fibrils; Amyloidogenesis; Coordination Complexes - chemistry; Disorders; dynamic light scattering; Electron microscopy; Fibrillogenesis; Fibrils; Fluorescence; Indoles - chemistry; Insulin; Insulin - chemistry; Kinetics; Light scattering; Magnesium; Magnesium - chemistry; Metalloporphyrins - chemistry; Particle Size; Photon correlation spectroscopy; phthalocyanines; porphyrazines; Porphyrins; Protein Aggregates; Proteins; Scanning electron microscopy; Zinc; Zinc - chemistry
• ISSN: 0952-3499; 1099-1352
• DOI: 10.1002/jmr.2660

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. Phthalocyanines and porphyrazines are studied as anti‐amyloidogenic agents on insulin model. Phthalocyanines and porphyrazines complexes differently affect the intensity and kinetic of amyloid aggregation and the morphology of fibrils; their effect depends on the nature of central metal and different spatial geometry of the macrocycles.