Promotion Effect of Succinimide on Amyloid Fibrillation of Hen Egg-White Lysozyme

Abstract

Amyloid fibrillation is closely associated with a series of neurodegenerative diseases. According to that, the intermediate soluble oligomers and protofibrils are more toxic; reducing their concentrations in protein solutions by accelerating fibrillation is believed as a feasible strategy for treatment or remission of the diseases. Using hen egg-white lysozyme (HEWL) as a model protein, the promotion effect of succinimide was revealed by a series of experiments, e.g., atomic force microscopy (AFM), thioflavin T (ThT) fluorescence assay, Far-UV circular dichroism (CD) and Raman spectroscopy, and modeling the effect of succinimide-like derivative intermediates of intramolecular deamidation of the backbone during amyloid fibrillation. The AFM measurement confirmed that succinimide effectively accelerated the morphological changes of HEWL, while at the molecular level, the accelerative transformation of protein secondary structures was also clarified by ThT fluorescence assay and Far-UV CD spectroscopy. The incubation time-dependent Raman spectroscopy further revealed that the direct transformation from α-helices to organized β-sheets occurred upon skipping the intermediate random coils under the action of succinimide. This “bridge” effect of succinimide was attributed to its special influence on disulfide bonds. In the presence of succinimide in protein solutions, the native disulfide bonds of lysozyme could be broken more efficiently and quickly within hydrolysis, resulting in exposure of the buried hydrophobic residues and accelerating the formation of cross β-sheet structures. The present investigation provides very useful information for understanding the effect of intramolecular deamidation on the whole amyloid fibrillation.

Picosecond Bessel Beam Fabricated Pure, Gold-Coated Silver Nanostructures for Trace-Level Sensing of Multiple Explosives and Hazardous Molecules

“…In this study, the recyclability of the fabricated AgNsS2 is elucidated, making it a potential candidate from a cost-effective application point of view. Furthermore, the versatility of response was reviewed while acquiring surface enhanced Raman signal with the same recycled AgNS2 substrate with HEWL protein biomolecule that exhibited prominent Raman peak at 1655 cm −1 up to 50 nM trace, one of lowest reported in the literature of the alike analyte molecule [81][82][83]. Comparing the SERS research data available on HEWL, only this molecule was probed for SERS studies utilizing Horiba micro-Raman spectrometer (LabRAM HR Evolution), with 532 nm excitation, 50× objective, with 25% of total excitation power (~540 mW).…”

“…For the molecules of thiram, PA, MB we have obtained the highest EFs and smallest LODs among a horde of substrates [40][41][42][43][44][45][46][47][48][49]68,69,[79][80][81][82][83] investigated by our group in the last 10 years.…”

Iodo-sulphonylation of 1,6-enynones: a metal-free strategy to synthesizeN-substituted succinimides

“…Among them, succinimides are one of the important structural motifs with widespread biological and pharmaceutical activities 4 d – e as well as drug candidates. 5 For instance Liu et al (2019) reported the promotional effect of succinimide on amyloid fibrillation of HEWL (Hen Egg-White Lysozyme) 6 and several other reports also disclosed the use of succinimide derivatives as anticonvulsant drugs. 7 Although several routes have emerged for the synthesis of succinimide motifs, 8 the development of a new synthetic methodology which is much simpler than the existing ones is always an interesting area of research considering the various biological properties exhibited by succinimides.…”

Silver-Catalyzed Radical Cascade Sulfonation/Cycloaddition for the Construction of Multifunctional Succimides Containing Separable Z/E-Isomers

“…The succimide motif is an intriguing member of N -containing heterocycles, pervasively presenced in natural active compounds, and a key reagent in synthetic chemistry . In addition, several succimide compounds have been used as medicine candidates for the promotion effect on amyloid fibrillation, treatment with neurodegenerative diseases, and anticonvulsant activity . Although a series of achievements were obtained, it still draws much attention to develop the concise and efficient stratagem for the construction of succimide scaffolds by employing readily available and inexpensive agents.…”