Two novel dipeptidyl peptidase-IV (DPP-IV) inhibitory peptides identified from truffle (Tuber sinense) by peptidomics, in silico, and molecular docking analysis

The aim of present study is to explore the endogenous dipeptidyl peptidase-IV (DPP-IV) inhibitory peptides from the edible truffle species Tuber sinense. The 4038 endogenous peptides from fresh ascocarps were identified using a peptidomics analysis based on the ultra-performance liquid chromatography-quadrupole-Orbitrap-tandem mass spectrometry (UPLC-Q-Orbitrap-MS2). Afterward, ten DPP-IV inhibitory peptides were screened through Peptide Ranker software and BIOPEP database. According to the absorption, distribution, metabolism, excretion, toxicities (ADMET) analysis and molecular docking analysis, two peptides (APIKIPVGPGTL and IEDP-DAPPPPPPREVIKN) were finally confirmed. The affinity values of APIKIPVGPGTL and IEDPDAPPPPPPREVIKN were -8.8 and -8.4 Kcal/mol, respectively. Two peptides had hydrogen bonds and hydrophobic interaction with amino acid residue in the S1 and S2 pockets of DPP-IV enzyme. Furthermore, the half-maximal inhibitory concentrations of two peptides were 643.14 +/- 1.79 mu M and 668.29 +/- 1.31 mu M, respectively. The oral glucose tolerance test (OGTT) of two peptides showed excellent hypoglycemic effect at 30 min after gavage. Our work may have important theoretical significance and practical value for further exploring the endogenous peptides of truffle species.