Examining the inhibitory actions of copolypeptides against amyloid fibrillogenesis of bovine insulin

• Published in: Biochemical engineering journal 2013-09, Vol.78, p.181-188
• Main Authors: Kao, Chen-Yuan, Lai, Jun-Kun, Lin, Ta-Hsien, Lin, Yu-Jiun, Jan, Jeng-Shiung, Wang, Steven S.-S.
• Format: Article
• Language: English
• Subjects: Aggregation; amyloid; Amyloid diseases; Amyloid fibril; Biological and medical sciences; Biophysical chemistry; Biotechnology; cattle; Fundamental and applied biological sciences. Psychology; hydrogen bonding; hydrophobic bonding; hydrophobicity; Inhibition; Insulin; noninsulin-dependent diabetes mellitus; phenylalanine; Polypeptides; Protein
• ISSN: 1369-703X; 1873-295X
• DOI: 10.1016/j.bej.2013.03.023

•Fibrillogenesis derived by bovine insulin can be attenuated by copolypeptides.•Copolypeptides concentration-dependently suppress the formation of insulin fibrils.•Extent of fibrillogenesis inhibition is correlated with the composition ratio in copolypeptide backbone. Amyloid fibrillogenesis has been involved in at least 40 different degenerative diseases. The 51-residue polypeptide hormone insulin, which is associated with type II diabetes, has been demonstrated to fibrillate in vitro. With bovine insulin as a model, the research presented here examines the influence of two simple, unstructured d,l-lysine-co-glycine (d,l-lys-co-gly) and d,l-lysine-co-L-phenylalanine (d,l-lys-co-phe) copolypeptides, on the in vitro fibril formation process of bovine insulin at pH 2.0 and 55°C. Our results showed that amyloid fibrillogenesis of insulin may be suppressed by both copolypeptides in a concentration-dependent fashion. In addition, the copolypeptides with higher molar fractions of glycine or l-phenylalanine residue, which are considered to possess higher hydrophobic interacting capacities, demonstrated the superior inhibitory potency against insulin fibril formation. Our findings suggest that the association of insulin and copolypeptides, which is likely dominated by hydrophobic interactions and hydrogen bonding, may mitigate the extent of insulin fibrillogenesis. We believe the results from this work may contribute to the understanding of the molecular factors affecting amyloid fibrillation and the molecular mechanism(s) of the interactions between the unstructured polypeptides and amyloid-forming proteins.