Mechanistic Insight into the Amyloid Fibrillation Inhibition of Hen Egg White Lysozyme by Three Different Bile Acids

The Journal of Physical Chemistry B, Journal Year: 2023, Volume and Issue: 127(10), P. 2198 - 2213

Published: March 2, 2023

Amyloid aggregation of protein is linked to many neurodegenerative diseases. Identification small molecules capable targeting amyloidogenic proteins has gained significant importance. Introduction hydrophobic and hydrogen bonding interactions through site-specific binding molecular ligand can effectively modulate the pathway. Here, we investigate possible roles three different bile acids, cholic acid (CA), taurocholic (TCA), lithocholic (LCA) with varying properties in inhibiting fibrillation. Bile acids are an important class steroid compounds that synthesized liver from cholesterol. Increasing evidence suggests altered taurine transport, cholesterol metabolism, synthesis have strong implications Alzheimer's disease. We find hydrophilic CA TCA (taurine conjugated form CA), substantially more efficient inhibitors lysozyme fibrillation than most secondary LCA. Although LCA binds strongly masks Trp residues prominently interactions, lesser extent at active site made a relatively weaker inhibitor HEWL TCA. The introduction greater number channels by several key amino which prone oligomers fibrils weakened protein's internal capabilities for undergoing amyloid aggregation.

Language: Английский

---

Amino Acid-Based Polymer-Coated Silver Nanoparticles as Insulin Fibril Inhibitors

ACS Applied Nano Materials, Journal Year: 2023, Volume and Issue: 6(10), P. 8705 - 8716

Published: May 16, 2023

To explore the impact of polymer-coated silver nanoparticles (PC-AgNPs) on extent insulin aggregation process, herein, we have synthesized three copolymers comprising poly(ethylene glycol) methyl ether methacrylate (PEGMA) and tert-butoxycarbonyl (Boc)-protected amino acid (alanine, leucine, phenylalanine) containing monomers, via reversible addition-fragmentation chain transfer (RAFT) polymerization. After deprotection Boc groups, as-prepared water-soluble were coated (Ag NPs), role these NPs pathways was examined by multifarious spectroscopic microscopic techniques. The inhibitory effect against fibrillation process found to be related surface properties NPs, with highest detected for phenylalanine-based Ag (PPhe-AgNPs). Using circular dichroism (CD) spectroscopy Nile red (NR) fluorescence spectroscopy, investigated conformational changes hydrophobic interaction in inhibiting upon treatment PC-AgNPs. Furthermore, PC-AgNPs also able disintegrate matured fibrils efficiently decreased fibril-induced cytotoxicity, as confirmed transmission electron microscopy (TEM) hemolysis study, respectively. Together, our findings established novel acid-based potent nanomaterials 77–96% fibril inhibition marked disaggregation fibrils.

Language: Английский

---

Glucagon: Delivery advancements for hypoglycemia management

International Journal of Pharmaceutics, Journal Year: 2024, Volume and Issue: 652, P. 123785 - 123785

Published: Jan. 13, 2024

Language: Английский

---

Impact of Confinement within a Hydrogel Mesh on Protein Thermodynamic Stability and Aggregation Kinetics

Molecular Pharmaceutics, Journal Year: 2024, Volume and Issue: 21(3), P. 1137 - 1148

Published: Jan. 26, 2024

Though protein stability and aggregation have been well characterized in dilute solutions, the influence of a confining environment that exists (e.g., intercellular tissue spaces therapeutic formulations) on structure is largely unknown. Herein, effects confinement were explored for proteins different sizes, stability, hydrophobicity when encapsulated hydrophilic poly(ethylene glycol) hydrogels. Denaturation curves show linear correlations between size (mesh size) thermodynamic i.e., unfolding free energy surface area accessible solvation (represented by m-value). Two clusters types are identifiable from these correlations; defined differences area, propensity. Proteins with higher larger lower propensity lysozyme myoglobin) less affected imposed mesh than smaller growth hormone aldehyde dehydrogenase). According to kinetics measured thioflavin T fluorescence, sizes resulted slower rates sizes. Compared buffer solution, hydrophobic human insulin) hydrogels accelerates aggregation. Conversely, amylin) decelerates or prevents aggregation, inversely proportional size. These findings provide new insights into conformational confined microenvironments relevant various cellular, tissue, therapeutics scenarios.

Language: Английский

---

Enhancing anti-amyloidogenic properties and antioxidant effects of Scutellaria baicalensis polyphenols through novel nanoparticle formation

International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: 262, P. 130003 - 130003

Published: Feb. 5, 2024

Language: Английский

---