1. Academic Validation
  2. Novel casein-derived immunomodulatory peptide PFPEVFG: Activity assessment, molecular docking, activity site and mechanism of action

Novel casein-derived immunomodulatory peptide PFPEVFG: Activity assessment, molecular docking, activity site and mechanism of action

  • J Dairy Sci. 2024 Jul 19:S0022-0302(24)01027-0. doi: 10.3168/jds.2024-25173.
Siyi Li 1 Yutong Jiang 1 Zhiqi Cao 1 Yanfeng Tuo 1 Guangqing Mu 1 Shujuan Jiang 2
Affiliations

Affiliations

  • 1 School of Food Science and Technology, Dalian Polytechnic University, Dalian, 116034, China.
  • 2 School of Food Science and Technology, Dalian Polytechnic University, Dalian, 116034, China. Electronic address: jianglaoda2005@126.com.
Abstract

Nowadays, there is still a gap in the knowledge of the structure-activity relationship of immunomodulatory Peptides. In this study, PFPEVFG was selected as a peptide with immunomodulatory activity from casein hydrolysate by virtual screening and its immunomodulatory activity was verified by the phagocytosis, proliferation, and expression of cytokines (IL-6, IL-1β, TNF-α) and chemokines (CXCL1, CXCL2) in RAW 264.7 macrophages. Next, molecular docking and double-stranded small interfering RNA (siRNA) mutually verified that the immunomodulatory activity of PFPEVFG was mediated by TLR2/4. Furthermore, the highest occupied molecular orbital (HOMO) analysis showed that the C19 = O20 site with a HOMO contribution of 32.22988% was its active site, and the phenylalanine, where the C19 = O20 site was located, was its active amino acid. Finally, the combination of pathway inhibitors and Western blot revealed that PFPEVFG activated macrophages through the nuclear factor-κB (NF-κB) signaling pathway. In summary, this study provided a new perspective on deeply understanding the structure-activity relationship of casein-derived immunomodulatory Peptides, as well as a further theoretical and technological basis for the application of immunomodulatory Peptides.

Keywords

Immunomodulatory peptide; molecular docking; signaling pathway; structure-activity relationship.

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