Identification and molecular docking of novel α-glucosidase inhibitory peptides from hydrolysates of Binglangjiang buffalo casein

Binglangjiang buffalo is a new type of river buffalo discovered in Tengchong of Yunnan Province, China, with rich protein in milk. In this study, we isolated novel alpha-glucosidase inhibitory peptides from the buffalo casein hydrolyzed by Dregea sinensis protease using RP-HPLC. A total of 26 peptides in the active fraction were identified by LC-MS/MS, mainly belonging to alpha(s1)-CN, alpha(s2)-CN, and beta-CN. Based on bioinformatics analysis, four peptides with potential alpha-glucosidase inhibitory activity were selected for chemical synthesis and activity verification. The four synthetic peptides exhibited alpha-glucosidase inhibitory activity and had IC(50)s of 470.492 +/- 3.086 mu mol/L (P3), 498.040 +/- 1.829 mu mol/L (P2), 503.635 +/- 3.269 mu mol/L (P1), and 542.502 +/- 1.995 mu mol/L (P4). Through molecular docking, we found that these four peptides may occupy the potential catalytic active sites (Arg387, Arg428, Arg727, Arg801, Arg799, and Trp710) of alpha-glucosidase through forming hydrogen bonds and hydrophobicity, thus hindering the formation of complex and glycosylation between alpha-glucosidase and substrate. Screening alpha-glucosidase from buffalo casein hydrolysates will provide insights for further study on the antidiabetic mechanism of the peptides and further development of antidiabetic functional food.

Automated summary

In this study, novel alpha-glucosidase inhibitory peptides were isolated from buffalo milk. Four synthetic peptides were found to have alpha-glucosidase inhibitory activity, hindering the formation of complex and glycosylation between alpha-glucosidase and substrate. The study provides insights for understanding the antidiabetic mechanism of the peptides and the development of antidiabetic functional food.