Wheat germ peptides (WGPs) have various benefits to human health, while their antidiabetes mechanism remains unknown. In this study, the α-glucosidase inhibition activity of WGPs was identified, exhibiting an IC value of 6.87 mg/mL. By further filtrating them into five groups according to molecular weight (), the fraction with < 1 kDa displayed the highest inhibitory activity with an IC of 2.10 mg/mL. The addition of 2 mg/mL WGPs with < 1 kDa effectively reduced the glucose-releasing rate on everted intestine sleeves. By virtual screening and HPLC-QTOF-MS/MS, LDLQR, AGGFR, and LDNFR were identified and synthesized for the first time, and their IC values were 8.59, 8.66, and 9.21 mM, respectively. Molecular docking and amino acid composition analysis results showed that the high content of C-terminal Arg residues in the peptides could be the essential reason for their α-glucosidase inhibition activity. This study paved a way to utilize WGPs as potential antidiabetes ingredients for the food industry.
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