Researchers at NIT Trichi have discovered that bile acids, specifically cholic acid (CA) and taurine conjugated form of cholic acid (TCA), have the potential to inhibit amyloid fibrillation, a process in which native soluble proteins misfold into insoluble fibrillar aggregates with cross-sheet structures. The study found that bile acids act as small molecular inhibitors for the fibrillogenesis of hen egg white lysozyme (HEWL) and that the more hydrophilic bile acids, CA and TCA, were more efficient inhibitors than the hydrophobic bile acid LCA. The difference in inhibition efficiency was attributed to the bile acids’ varying hydrophobic-hydrophilic balance and their interactions with key amino acid residues at the active site of HEWL. This discovery could lead to the development of bile acid-based therapeutic approaches for diseases associated with amyloid fibrillation.
A recent study by Sonea, Branch, and Warren found that the pattern of hydroxyphenyl-substitution has a stronger influence on CO2 reduction than the number of hydroxyphenyl groups in iron-porphyrin electrocatalysts. The study showed that the addition of acid is important to observe increases in catalytic current when catalysts do not have adjacent meso dihydroxyphenyl groups. Additionally, the study found that the geometry of the OH groups is more important for CO2 reduction activity than the electronic effects of meso substitutions. The study also revealed that the intramolecular proton source contribution of adjacent meso-2,6-dihydroxyphenyl groups was observed for both FeTPP and FeTPP4 catalysts. This research could aid in the development of more efficient CO2 reduction catalysts.
The Pattern of Hydroxyphenyl-Substitution Influences CO 2 Reduction More Strongly than the Number of Hydroxyphenyl Groups in Iron-Porphyrin Electrocatalysts
Sonea; Branch; Warren
Full-text link: https://doi.org/10.1021/acscatal.2c06275
What this paper is about
- In the cases where the catalysts do not have adjacent meso dihydroxyphenyl groups, the greater difference in i cat /i p 0 between the absence and presence of PhOH shows that the addition of acid is important to observe increases in catalytic current.
- FeTPP 4 catalyst shows larger i cat /i p 0 values than for FeTPP, despite the FeC vibrational stretch being smaller in the former. These results suggest that the geometry of the OH groups is more important for CO 2 reduction activity than the electronic effects of these the meso substitutions.
- Specifically, the hydrogen bonding of the hydroxyphenyl groups with the bound-CO 2 plays an important role in the net CO 2 reduction reaction, but the adjacent meso substitutions can further improve catalysis by providing an intramolecular proton source.
What you can learn
- The systematic addition of the 2,6-dihydroxyphenyl groups allows for analysis of relative potentials and for computational analysis of CO 2 binding. This revealed a scaling relationship with respect to both Fe I/0 formal potentials and the calculated FeC vibrational frequencies in the.
- While the FeTPP complex is easier to reduce to the active Fe 0 state, it is at the cost of CO 2 reduction kinetics. This is not the case in a catalyst related to trans.
- The intramolecular proton source contribution of these adjacent meso-2,6-dihydroxyphenyl groups was also observed for FeTPP and FeTPP catalysts.
Core Q&A related to this research
What is amyloid fibrillation and how have bile acids been studied in relation to it?
Answer: Amyloid fibrillation is the process in which native soluble proteins misfold into insoluble fibrillar aggregates with cross-sheet structures. Bile acids are a particular class of amphiphilic steroid molecules that have been extensively studied as small molecular inhibitors for the fibrillogenesis of a model protein called hen egg white lysozyme (HEWL).
Which bile acids were studied in relation to the inhibition of HEWL amyloid fibrillation?
Answer: Three different bile acids were studied: CA, TCA (taurine conjugated form of cholic acid), and LCA.
What techniques were used to explore the binding modes of the three fatty acids to target hexoprotein in the native form under physiological pH at room temperature, as well as in a partially unfolded form under pH 2.0 at 55 °C?
Answer: Molecular dynamics simulation and docking studies were used to explore the binding modes of the three fatty acids.
What observations were made regarding the inhibitory effect of LCA on the hematoxylin-eosin (ThT) fibril formation, and how was it achieved?
Answer: The inhibitory effect of LCA on ThT fibril formation can be achieved through an appropriate balance of both hydrophobic and hydrogen bonding interactions with the protein.
What is the main finding of the research paper titled “The Pattern of Hydroxyphenyl-Substitution Influences CO2 Reduction More Strongly than the Number of Hydroxyphenyl Groups in Iron-Porphyrin Electrocatalysts”?
Answer: The geometry of the OH groups is more important for CO2 reduction activity than the electronic effects of the meso substitutions in iron-porphyrin electrocatalysts. The hydrogen bonding of the hydroxyphenyl groups with the bound-CO2 plays an important role in the net CO2 reduction reaction, but the adjacent meso substitutions can further improve catalysis by providing an intramolecular proton source.
Basics Q&A related to this research
- What is amyloid fibrillation?
Amyloid fibrillation is a process in which native soluble proteins are misfolded into insoluble fibrillar aggregates with cross-sheet structures.
- What are bile acids?
Bile acids are a particular class of amphiphilic steroid molecules that are having multiple protein targeting sites.
- What is the role of bile acids in the inhibition of protein fibrillation?
Bile acids have been extensively studied as small molecular inhibitors for the fibrillogenesis of a model protein hen egg white lysozyme (HEWL).
- What is hexoprotein?
Hexoprotein is a target protein that has been used to investigate the possible roles of different bile acids in the inhibition of amyloid fibrillation.
- What methods have been used to explore the binding modes of bile acids to target hexoprotein?
Molecular dynamics simulation and docking studies have been used to explore the binding modes of three different bile acids (CA, TCA, and LCA) to target hexoprotein.
- What techniques have been used to examine the conformational changes associated with the formation of nonfibrillar spherical aggregates?
FTIR spectroscopy and TEM analysis have been performed to examine the conformational changes associated with the formation of many nonfibrillar spherical aggregates (as evidenced by the X-ray diffraction spectra of ThT).
- What is Trp fluorescence?
Trp fluorescence is a technique used to measure the binding interactions (hydrophobic, hydrogen bonding, and other weak van der Waals interactions) of bile acids with key amino acid residues at the active site of HEWL.
- What are hydrophobic and hydrogen bonding interactions?
Hydrophobic interactions involve the attraction or repulsion between nonpolar molecules or nonpolar regions of the same molecule, while hydrogen bonding interactions involve the attraction between a partially positively charged hydrogen atom and a partially negatively charged atom (usually oxygen or nitrogen) of another molecule.
- What are inhibition efficiencies?
Inhibition efficiencies refer to the ability of different bile acids to inhibit the formation of protein fibrils.
- What is the difference between hydrophilic and hydrophobic bile acids in their inhibitory effect on protein fibrillation?
The relatively more hydrophilic bile acids CA and TCA are more efficient inhibitors than the hydrophobic bile acid LCA. The difference in inhibition efficiencies of the three bile acids on HEWL fibrillation is found to be associated with the difference in their binding interactions with the protein.
- What is the hydrophobic surface of bile acids?
The hydrophobic surface of bile acids refers to the nonpolar surface of the molecule that helps in stabilizing partially unfolded protein structures by binding with the exposed hydrophobic protein surface and minimizing its contact with the bulk solvent.
- What is a therapeutic approach using bile acid derivatives?
A therapeutic approach using bile acid derivatives involves manipulating the hydrophobic and hydrogen bonding properties of bile acids to develop bile acid-based therapies for amyloid fibrillation and other protein misfolding disorders.
