Myricetin and morin hydrate inhibit amyloid fibril formation of bovine α-lactalbumin (BLA).

Amyloid fibrils are self-assembled aggregates of proteins and peptides that can lead to a broad range of diseases called amyloidosis. So far, no definitive and approved treatment to target directly amyloid fibrils has been introduced. Nevertheless, the search for small molecules with ability to inhibit and suppress fibril formation is an active and promising area of the research. Herein, the binding interactions and inhibitory effects of myricetin and morin hydrate on the in vitro fibrillation of bovine α-lactalbumin (BLA) have been investigated. The intrinsic fluorescence of BLA was quenched by myricetin and morin hydrate through combination of the static and dynamic quenching along with non-radiative Förster energy transfer mechanisms. The binding of these two flavonoids to BLA were not accompanied by major alteration in the conformation of BLA as evidenced by CD studies. The results of the fluorescence quenching analyses indicated almost the same binding affinities of myricetin and morin hydrate toward BLA (Kb ~ 106 M-1). However, the results of thioflavin T (ThT) assays showed that myricetin is a stronger inhibitor against BLA fibrillation compared to morin hydrate.

Interaction of gallium, indium, and vanadyl curcumin complexes with hen egg-white lysozyme (HEWL): Mechanistic aspects and evaluation of antiamyloidogenic activity.

Many proteins and peptides can aggregate into amyloid fibrils with high-ordered and cross-ß rich structure characteristics. Amyloid deposition is a common feature of neurodegenerative diseases called amyloidosis. Various natural polyphenolic compounds such as curcumin exhibited antiamyloidogenic activities, but less researches were focused on the metal complexes of these compounds. In this study, the inhibitory effects of gallium curcumin (Ga(cur)3), indium curcumin (In(cur)3), and vanadyl curcumin (VO(cur)2) on the amyloid fibrillation of hen egg white lysozyme (HEWL) have been investigated. Moreover, the details of binding interactions of these metal complexes with HEWL have been explored. The results of fluorescence quenching analyses revealed that In(cur)3 and VO(cur)2 have much higher binding affinities than Ga(cur)3 toward HEWL. The interactions of these metal complexes were accompanied by partial conformational changes in the tertiary structure of HEWL. The kinetic curves of the fibrillation process demonstrated that In(cur)3 and VO(cur)2 have higher inhibitory effects than Ga(cur)3 on the amyloid fibrillation of HEWL. The strength of binding to HEWL is completely in accordance with inhibitory activities of these metal complexes of curcumin.

Interaction of gallium, indium and vanadyl diacetylcurcumin complexes with lysozyme: mechanistic aspects and evaluation of antiamyloidogenic activity.

Diacetylcurcumin as a derivative of curcumin is a strong nitric oxide (NO) and O2-.anion scavenger. One strategy to improve stability of curcumin and its derivatives is complexation with metal. In this study, the binding interactions of gallium diacetylcurcumin (Ga(DAC)3), indium diacetylcurcumin (In(DAC)3), and vanadyl diacetylcurcumin (VO(DAC)2) with hen egg white lysozyme (HEWL) have been investigated. The results of fluorescence quenching analyses revealed that In(DAC)3 and VO(DAC)2 have higher binding affinities than Ga(DAC)3 towards HEWL. The interactions of these metal complexes were not accompanied by considerable conformational changes in the tertiary structure of HEWL. Furthermore, the inhibitory effects of these complexes on the amyloid fibrillation of HEWL were confirmed by the thioflavin T fluorescence assays. The kinetic curves of the fibrillation process illustrated that VO(DAC)2 has the highest inhibitory activity and In(DAC)3 has a significant delaying effect on the formation of amyloid fibrils of HEWL.

Formation of a Highly Stable and Nontoxic Protein Corona upon Interaction of Human α-1-Acid Glycoprotein (AGP) with Citrate-Stabilized Silver Nanoparticles.

Given the importance of protein corona in determining cellular responses to nanoparticles, numerous studies have been devoted to finding stable, biocompatible, and nontoxic protein corona. In this work, the interaction between human α-1-acid glycoprotein (AGP) and citrate-stabilized silver (Ag-CIT) nanoparticles of about 10 nm was methodically studied using molecular docking simulation approach and various experimental techniques. It could be shown that a stable Ag-CIT/AGP bioconjugate was formed with a high binding constant of 109 M-1, several orders of magnitude larger than that of other highly abundant serum proteins. Formation of AGP corona was accompanied by conserving the native conformation of the protein and further associated with a considerable decrease in the cytotoxicity of the silver nanoparticles.