Virtual Screening and Mechanism of Action of DPP-IV Inhibitory Peptides from <i>Pinctada fucata </i>(<i>P. fucata</i>)

LI Jiao; SU Jilei; CHEN Min; DAI Shikun; GAO Yongli; YIN Hao

doi:10.13386/j.issn1002-0306.2020120273

Volume 42 Issue 16

Aug. 2021

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Science and Technology of Food Industry > 2021 > 42(16): 1-7. > DOI: 10.13386/j.issn1002-0306.2020120273

LI Jiao, SU Jilei, CHEN Min, et al. Virtual Screening and Mechanism of Action of DPP-IV Inhibitory Peptides from Pinctada fucata (P. fucata)[J]. Science and Technology of Food Industry, 2021, 42(16): 1−7. (in Chinese with English abstract). doi: 10.13386/j.issn1002-0306.2020120273.

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Virtual Screening and Mechanism of Action of DPP-IV Inhibitory Peptides from Pinctada fucata (P. fucata)

LI Jiao^{1, 2, 3,},
SU Jilei^{1, 2, 3},
CHEN Min^{1, 2, 3},
DAI Shikun^{1, 3},
GAO Yongli^{1, 3},
YIN Hao^{1, 3, ,}

1.
The Equipment Public Service Center, CAS Key Laboratory of Tropical Marine Bio-resources and Ecology, Chinese Academy of Sciences, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China
2.
University of Chinese Academy of Sciences, Beijing 100049, China
3.
Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou), Guangzhou 511458, China

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Received Date: December 29, 2020
Available Online: June 07, 2021

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Abstract

Abstract

In order to discover the dipeptidyl peptidase IV (DPP-IV) peptides quickly from Pinctada fucata (P. fucata), in this research, 20 reported DPP-IV inhibitory peptides in the database were used to form a training set and construct pharmacophore models, which were then valuated by test set molecules and fisher random validation. The online website PeptideCutter was employed to perform the virtual hydrolysis with P. fucata meat protein as raw materials. The optimal pharmacophore model (Hypo1) was used to initially screen the 192 low-molecular peptides (the number of amino acids was no more than 5), which were obtained by the virtual hydrolysis, and then the molecular docking was performed for further screening. Furthermore, the potential DPP-IV inhibitory peptides were synthesized using a solid-phase method, and their activities were verified in vitro and the interaction mechanism was analyzed. The results showed that 4 potential DPP-IV inhibitory peptides, namely LPIY, VQDR, PIY, and APSL were screened through pharmacophore combined with molecule docking. Among them, VQDR and PIY did not show inhibitory activity, while LPIY and APSL had strong DPP-IV inhibitory activity, with IC₅₀ values of 521.19 and 258.67 µmol/L respectively. The interaction mechanism indicated both peptides formed multiple hydrogen bonds with the amino acid residues within the active pocket of DPP-IV, and the proline (P) at the second position of the N-terminal constructed Pi-Alkyl interactions with the residues of the active pocket, which promoted the DPP-IV inhibitory activity for LPIY and APSL. The current work would provide a theoretical method for screening DPP-IV inhibitory peptides derived from P. fucata efficiently.
- Pinctada fucata (P. fucata),
- dipeptidyl peptidase IV (DPP-IV),
- pharmacophore model,
- peptides,
- molecular docking

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References (29)

References

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