Inhibition of insulin fibrillation by carboxyphenylboronic acid-modified chitosan oligosaccharide based on electrostatic interactions and hydrophobic interactions

Biophys Chem. 2024 Apr 8;310:107236. doi: 10.1016/j.bpc.2024.107236. Online ahead of print.ABSTRACTA novel inhibitor, carboxyphenylboronic acid-modified chitosan oligosaccharide (COS-CPBA), was developed by coupling carboxyphenylboronic acid (CPBA) with chitosan oligosaccharide (COS) to inhibit insulin fibrillation. Extensive biophysical assays indicated that COS-CPBA could decelerate insulin aggregation, hinder the conformational transition from α-helix to β-sheet structure, change the morphology of insulin aggregates and alter fibrillation pathway. A mechanism for the inhibition of insulin fibrillation by COS-CPBA was proposed. It considers that insulin molecules bind to COS-CPBA via hydrophobic interactions, while the positively charged groups in COS-CPBA exert electrostatic repulsion on the bound insulin molecules. These two opposite forces cause the insulin molecules to display extended conformations and hinder the conformational transition of insulin from α-helix to β-sheet structure necessary for fibrillation, thus decelerating aggregation and altering the fibrillation pathway of insulin. The studies provide novel ideas for the development of more effective inhibitors of amyloid fibrillation.PMID:38615538 | DOI:10.1016/j.bpc.2024.107236

Source: Biophysical Chemistry - April 14, 2024 Category: Chemistry Authors: Xiangyuan Zhao Chunyan Yang Wei Liu Ke Lu Hao Yin Source Type: research