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

Abstract

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 α-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 αs1-CN, αs2-CN, and β-CN. Based on bioinformatics analysis, four peptides with potential α-glucosidase inhibitory activity were selected for chemical synthesis and activity verification. The four synthetic peptides exhibited α-glucosidase inhibitory activity and had IC50s of 470.492 ± 3.086 μmol/L (P3), 498.040 ± 1.829 μmol/L (P2), 503.635 ± 3.269 μmol/L (P1), and 542.502 ± 1.995 μmol/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 α-glucosidase through forming hydrogen bonds and hydrophobicity, thus hindering the formation of complex and glycosylation between α-glucosidase and substrate. Screening α-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.