Biochemical and Biophysical Research Communications
Contribution of simple saccharides to the stabilization of amyloid structure
Section snippets
Materials and methods
Peptides. Aβ40/42 were synthesized by solid phase Fmoc-chemistry by the Hospital for Sick Children’s Biotechnology Centre (Toronto, Ont., Canada). They were purified by reverse phase HPLC on a C18 μbondapak column. Aβ peptides were initially dissolved in 0.5 ml of 100% trifluoroacetic acid (Aldrich Chemicals, Milwaukee, WI) to ensure that the peptide remained monomeric and free of fibril seeds, diluted in distilled H2O, and immediately lyophilized [14]. Aβ peptides were then dissolved at 1 mg/ml
Cosolvent-induced secondary structural transitions of Aβ40/42
In order to address the role of osmolyte–peptide interactions from macromolecular crowding, we chose to examine a series of monosaccharides with identical molecular weights, similar hydrodynamic volumes, and hard sphere radii (Table 1). This series of monosaccharides allowed us to dissect properties important for the stability and kinetics of peptide folding. We have also included the disaccharide, sucrose, which is comprised of two of the monosaccharides examined and has been previously shown
Conclusions
Many studies have shown that the distribution of H-bonding partners across a compound will determine the interaction with amyloid forming proteins/peptides [22], [23]. Sugar cosolvents replace hydrogen-bonded water molecules, which are important for protein stability, therefore structural stability is determined by the hydrogen bond potential of the sugar [24]. The less mobile sugars would be expected to form more stable, stronger hydrogen bonds, and therefore increase native protein stability
Acknowledgments
The authors acknowledge support from the Ontario Alzheimer’s Society (J.M.), Canadian Institutes of Health Research (J.M.), Natural Science and Engineering Research Council of Canada (J.M.), and Scottish and Cryptic Rite Charitable Foundations (J.M.).
References (24)
Effect of a concentrated “inert” macromolecular cosolute on the stability of a globular protein with respect to denaturation by heat and by chaotropes: A statistical-thermodynamic model
Biophys. J.
(2000)Macromolecular crowding: Obvious but underappreciated
Trends Biochem. Sci.
(2001)- et al.
Manipulation the amyloid-β aggregation pathway with chemical chaperones
J. Biol. Chem.
(1999) - et al.
Macromolecular crowding accelerates amyloid formation by human apolipoprotein C-II
J. Biol. Chem.
(2002) - et al.
Counteracting effects of renal solutes on amyloid fibril formation by immunoglobulin light chains
J. Biol. Chem.
(2001) - et al.
Multiple effects of trehalose on protein folding in vitro and in vivo
Mol. Cell
(1998) - et al.
Amyloid-β interactions with chondroitin sulfate-derived monosaccharides and disaccharides. Implications for drug development
J. Biol. Chem.
(2001) - et al.
Hydrogen bonding between sugar and protein is responsible for inhibition of dehydration-induced protein unfolding
Arch. Biochem. Biophys.
(1999) - et al.
Probing protein–sugar interactions
Biophys. J.
(2000) - et al.
Solute excluded-volume effects on the stability of globular proteins: A statistical-thermodynamic theory
Biopolymers
(1996)
Sugar-induced molten-globule model
Biochemistry
Interpreting the effects of small uncharged solutes on protein-folding equilibria
Annu. Rev. Biomol. Struct.
Cited by (54)
Sugar osmolyte inhibits and attenuates the fibrillogenesis in RNase A: An in vitro and in silico characterizations
2023, International Journal of Biological MacromoleculesOsmolytes: Wonder molecules to combat protein misfolding against stress conditions
2023, International Journal of Biological MacromoleculesUsing Sugar-Derived Nanoparticles to Mitigate Amyloid Fibril Formation of Lysozyme
2022, Journal of the Taiwan Institute of Chemical EngineersCitation Excerpt :Additionally, the positive values of enthalpy change and entropy change suggest that the binding is predominantly driven by the hydrophobic interactions [43]. The results from previous studies suggested that the binding between sugars and polypeptides may involve two processes: (1) the interaction between the hydrophobic rings of sugars and hydrophobic area of proteins and (2) the stabilization by hydrogen bonding. [44] In addition, evidence indicated that the microenvironment of tryptophan residues of proteins tended to be more hydrophobic than the solvent environment [33].
Investigating the effect of sugar-terminated nanoparticles on amyloid fibrillogenesis of β-lactoglobulin
2020, International Journal of Biological Macromolecules