Molecular mechanisms of novel peptides from silkworm pupae that inhibit α-glucosidase

The objectives of this study were to identify peptides that inhibit alpha-glucosidase using a quantitative structure-activity relationship (QSAR) screening method and a database of silkworm peptides. This study compared the docking characteristics of several peptides with high inhibitory activity against alpha-glucosidase and summarized the molecular mechanisms by which the silkworm peptides affected alpha-glucosidase. Four peptides that strongly inhibited alpha-glucosidase were obtained: Gln-Pro-Gly-Arg with IC50 at 65.8 mu mol/L, Ser-Gln-Ser-Pro-Ala at 20 mu mol/L, Gln-Pro-Pro-Thr at 560 mu mol/L and Asn-Ser-Pro-Arg at 205 mu mol/L. Studies docking the peptides to the active site of alpha-glucosidase (PDB ID: 2QMJ) showed that a common characteristic was Lys776 in 2QMJ, which could be a critical target for alpha-glucosidase trapping of inhibitory peptides. The results revealed that the four peptides, especially Ser-Gln-Ser-Pro-Ala, could be potential drugs for treating diabetes. (C) 2015 Elsevier Inc. All rights reserved.