Academic Journal
Quantum-chemistry-guided identification of a dual-functional cod-derived peptide targeting oxidative stress and inflammation.
| Τίτλος: | Quantum-chemistry-guided identification of a dual-functional cod-derived peptide targeting oxidative stress and inflammation. |
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| Συγγραφείς: | Xin XY; Engineering Research Center of North-East Cold Region Beef Cattle Science & Technology Innovation, Ministry of Education, Jilin Beef Cattle Science and industrial technology major demand collaborative Innovation Center, Department of Animal Science, Yanbian University, Yanji, 133002, China., Park S; Department of Food Science and Biotechnology, Sejong University, Seoul, 05006, Republic of Korea., Wang HW; Engineering Research Center of North-East Cold Region Beef Cattle Science & Technology Innovation, Ministry of Education, Jilin Beef Cattle Science and industrial technology major demand collaborative Innovation Center, Department of Animal Science, Yanbian University, Yanji, 133002, China., Hur S; Department of Animal Science and Technology, Chung-Ang University, Anseong, 17546, Republic of Korea., Li XZ; Engineering Research Center of North-East Cold Region Beef Cattle Science & Technology Innovation, Ministry of Education, Jilin Beef Cattle Science and industrial technology major demand collaborative Innovation Center, Department of Animal Science, Yanbian University, Yanji, 133002, China. Electronic address: lxz@ybu.edu.cn., Choi S; Department of Animal Science, Chungbuk National University, Cheongju, 28644, Republic of Korea. Electronic address: seongho@cbnu.ac.kr. |
| Πηγή: | Bioorganic chemistry [Bioorg Chem] 2026 Aug 15; Vol. 178, pp. 109963. Date of Electronic Publication: 2026 May 08. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Elsevier Country of Publication: United States NLM ID: 1303703 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1090-2120 (Electronic) Linking ISSN: 00452068 NLM ISO Abbreviation: Bioorg Chem Subsets: MEDLINE |
| Imprint Name(s): | Publication: Amsterdam : Elsevier Original Publication: New York, London, Academic Press. |
| Ιατρικοί όροι (MeSH): | Oxidative Stress*/drug effects , Inflammation*/drug therapy , Inflammation*/metabolism , Peptides*/chemistry , Peptides*/pharmacology , Quantum Theory*, Lipopolysaccharides/pharmacology ; Lipopolysaccharides/antagonists & inhibitors ; Toll-Like Receptor 4/metabolism ; Animals ; Mice ; RAW 264.7 Cells ; Structure-Activity Relationship ; Molecular Structure ; Dose-Response Relationship, Drug ; Molecular Docking Simulation ; Density Functional Theory |
| Περίληψη: | Objective: To identify dual-functional peptides from cod protein targeting oxidative stress and inflammation by investigating their electronic structure-activity relationships through an integrated computational and experimental approach. Methods: From 1206 in silico hydrolyzed cod peptides, candidates were screened via dual-target docking (Keap1/TLR4), DFT calculations, and MD simulations, followed by validation in LPS-induced RAW264.7 cells. Results: The tetrapeptide YGDF was identified as a lead candidate. In silico analysis predicted that the tetrapeptide YGDF possesses a strong electron-donating propensity due to its unique electronic topology. Fukui function analysis suggested a 'nucleophilic-electrophilic' dual-center distribution, where the Tyr1 site acts as a radical scavenger while the Asp3/Phe4 residues facilitate anchoring within the TLR4 binding pocket. Experimental validation confirmed that YGDF (100 μg/mL) effectively suppressed the NF-κB inflammatory cascade and activated the Nrf2 antioxidant pathway in LPS-induced RAW264.7 cells. Specifically, YGDF inhibited the mRNA expression of iNOS and COX-2 by approximately 75% and 80%, respectively, and induced a 30-fold increase in HO-1 transcription. Conclusion: YGDF acts as a dual-target regulator, and its bioactivity is closely associated with the electronic spatial distribution predicted by Fukui function analysis. (Copyright © 2026 Elsevier Inc. All rights reserved.) |
| Competing Interests: | Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. |
| Contributed Indexing: | Keywords: Anti-inflammatory peptides; Antioxidant peptides; Cod; Molecular simulation; Quantum chemistry |
| Substance Nomenclature: | 0 (Lipopolysaccharides) 0 (Peptides) 0 (Toll-Like Receptor 4) |
| Entry Date(s): | Date Created: 20260512 Date Completed: 20260716 Latest Revision: 20260716 |
| Update Code: | 20260717 |
| DOI: | 10.1016/j.bioorg.2026.109963 |
| PMID: | 42119211 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1090-2120 |
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| DOI: | 10.1016/j.bioorg.2026.109963 |