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Mining and validation of novel hemp seed-derived DPP-IV-inhibiting peptides using a combination of multi-omics and molecular docking
Hai-Hong Chena,b, Wei Lia, Yi Wangc, Bing Xua,b, Xi Hub, Xiao-Bing Lia, Jun-Yu Liua, Chong Zhangc,d, Can-Yang Zhanga, Xin-Hui Xinga,b,c,d*
a Institute of Biopharmaceutical and Health Engineering, Tsinghua Shenzhen International Graduate School, Shenzhen 518055, China
b Shenzhen Bay Laboratory, Institute of Biomedical Health Technology and Engineering, Shenzhen 440300, China
c Key Laboratory for Industrial Biocatalysis, Ministry of Education, Department of Chemical Engineering, Institute of Biochemical Engineering, Beijing 100084, China
d Center for Synthetic and Systems Biology, Tsinghua University, Beijing 100084, China
*Corresponding author.
Abstract
Hemp seed-derived inhibitors of dipeptidyl peptidase IV (DPP-IV) demonstrate potential as novel therapeutics for diabetes; however, their proteome and genome remain uncharacterized. We used multi-omics technology to mine peptides capable of inhibiting DPP-IV. First, 1261 and 1184 proteins were identified in fresh and dry hemp seeds, respectively. Simulated protease cleavage of dry seed proteins yielded 185,446 peptides for virtual screening to select the potential DPP-IV-inhibiting peptides. Sixteen novel peptides were selected according to their DPP-IV-binding affinity determined via molecular docking. In vitro DPP-IV inhibition assays identified the peptides LPQNIPPL, YPYY, YPW, LPYPY, WWW, YPY, YPF, and WS with half-maximal inhibitory concentration (IC50) values lower than 0.5 mM, which were 0.08 ± 0.01, 0.18 ± 0.03, 0.18 ± 0.01, 0.20 ± 0.03, 0.22 ± 0.03, 0.29 ± 0.02, 0.42 ± 0.03, and 0.44 ± 0.09 mM, respectively. The dissociation constants (KD) of the 16 peptides ranged from 1.50 × 10–4 to 1.82 × 10–7 M. Furthermore, Caco2 and INS-1 cell assays showed that all 16 peptides could efficiently inhibit DPP-IV activity and increase insulin and glucagon-like peptide-1 concentrations. These results demonstrate a well-established and efficient method to isolate food-derived therapeutic DPP-IV-inhibiting peptides.
CHEN H H, LI W, WANG Y, et al. Mining and validation of novel hemp seed-derived DPP-IV-inhibiting peptides using a combination of multi-omics and molecular docking[J]. Journal of Agricultural and Food Chemistry, 2023, 71, 9164–9174. DOI:10.1021/acs.jafc.3c00535.
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