Macrocyclic Cavitand β-Cyclodextrin Inhibits the Alcohol-Induced Trypsin Aggregation.

Area of Science:

• Biochemistry
• Molecular Biology
• Medical Chemistry

Background:

• Trypsin, a key pancreatic protein, aids digestion but aggregates with alcohol, potentially causing pancreatitis and cancer.
• Alcohol-induced trypsin aggregation leads to loss of function and fibril formation.

Purpose of the Study:

• To investigate the inhibitory effect of beta-cyclodextrin (β-CD) on alcohol-induced trypsin aggregation.
• To elucidate the mechanism of inhibition using experimental and theoretical methods.

Main Methods:

• Fluorescence Correlation Spectroscopy (FCS)
• Circular Dichroism (CD) spectroscopy
• Molecular docking and simulation studies

Main Results:

• Beta-cyclodextrin (β-CD) effectively inhibits trypsin aggregation in a dose-dependent manner.
• β-CD preserves trypsin's secondary structure and prevents fibril formation.
• Spectroscopic and simulation data confirm the inhibition of aggregation and identify key residues involved.

Conclusions:

• Beta-cyclodextrin (β-CD) is a potent inhibitor of alcohol-induced trypsin aggregation.
• This study provides a molecular basis for β-CD's protective effects against alcohol-related pancreatic damage.
• Findings suggest potential therapeutic applications of β-CD in preventing pancreatitis and pancreatic cancer.