{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T06:35:35Z","timestamp":1787726135053,"version":"build-2784847793"},"reference-count":70,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T00:00:00Z","timestamp":1761868800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["22378368"],"award-info":[{"award-number":["22378368"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"\u201cPioneer\u201d and \u201cLeading Goose\u201d R&D Program of Zhejiang","award":["2025C01099"],"award-info":[{"award-number":["2025C01099"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Foods"],"abstract":"<jats:p>The relationship between the structure of walnut-derived peptides and their activity of transport efficiency across the blood\u2013brain barrier (BBB) remains unclear. In this study, a series of walnut-derived peptides were synthesized by substituting leucine (L) with tyrosine (Y), lysine (K), or arginine (R). Three outstanding peptides\u2014EVSGPGYSPN, TWLPYPR, and YVPFPYP\u2014were selected based on their antioxidant capacity and BBB transport efficiency, with EVSGPGYSPN exhibiting the highest activity. Reversed-phase high-performance liquid chromatography (RP-HPLC) and Transwell assay results demonstrated that EVSGPGYSPN can remain stable during gastrointestinal digestion and penetrate the BBB. Pharmacokinetic results revealed that the cumulative concentration of EVSGPGYSPN in the brain reached 1.25 \u00b1 0.91 \u00b5g\/g at 10 h, while its plasma half-life exceeded 12 h. Furthermore, it significantly reduced reactive oxygen species (ROS) levels to 110.46 \u00b1 15.16%. Nuclear magnetic resonance (NMR) and Fourier-transform infrared spectroscopy (FTIR) results indicated that EVSGPGYSPN is rich in aromatic hydrogen signals and exhibits low methyl signals, which may enhance its antioxidant activity. Circular dichroism (CD) spectroscopy showed that EVSGPGYSPN has the highest random coil content, which facilitates its binding to transporters on the BBB and promotes BBB permeability. This study provides valuable insights into the design of brain-targeted peptide delivery systems.<\/jats:p>","DOI":"10.3390\/foods14213744","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T14:40:48Z","timestamp":1762180848000},"page":"3744","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Structural Engineering of Tyrosine-Based Neuroprotective Peptides: A New Strategy for Efficient Blood\u2013Brain Barrier Penetration"],"prefix":"10.3390","volume":"14","author":[{"given":"Zehui","family":"Li","sequence":"first","affiliation":[{"name":"National Key Laboratory for Development and Utilization of Forest Food Resources, Zhejiang A&F University, Hangzhou 311300, China"},{"name":"College of Food Science and Engineering, Jilin Agricultural University, Changchun 130118, China"},{"name":"College of Food and Health, Zhejiang A&F University, Hangzhou 311300, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiyue","family":"Zhu","sequence":"additional","affiliation":[{"name":"National Key Laboratory for Development and Utilization of Forest Food Resources, Zhejiang A&F University, Hangzhou 311300, China"},{"name":"College of Food and Health, Zhejiang A&F University, Hangzhou 311300, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yashu","family":"Qiao","sequence":"additional","affiliation":[{"name":"National Key Laboratory for Development and Utilization of Forest Food Resources, Zhejiang A&F University, Hangzhou 311300, China"},{"name":"College of Food and Health, Zhejiang A&F University, Hangzhou 311300, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junxi","family":"Fu","sequence":"additional","affiliation":[{"name":"National Key Laboratory for Development and Utilization of Forest Food Resources, Zhejiang A&F University, Hangzhou 311300, China"},{"name":"College of Food Science and Engineering, Jilin Agricultural University, Changchun 130118, China"},{"name":"College of Food and Health, Zhejiang A&F University, Hangzhou 311300, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1529-5732","authenticated-orcid":false,"given":"Li","family":"Tao","sequence":"additional","affiliation":[{"name":"National Key Laboratory for Development and Utilization of Forest Food Resources, Zhejiang A&F University, Hangzhou 311300, China"},{"name":"College of Food and Health, Zhejiang A&F University, Hangzhou 311300, China"},{"name":"Provincial Key Laboratory for Non-Wood Forest and Quality Control and Utilization of Its Products, Zhejiang A&F University, Hangzhou 311300, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weihong","family":"Min","sequence":"additional","affiliation":[{"name":"National Key Laboratory for Development and Utilization of Forest Food Resources, Zhejiang A&F University, Hangzhou 311300, China"},{"name":"College of Food and Health, Zhejiang A&F University, Hangzhou 311300, China"},{"name":"Provincial Key Laboratory for Non-Wood Forest and Quality Control and Utilization of Its Products, Zhejiang A&F University, Hangzhou 311300, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"170571","DOI":"10.1016\/j.peptides.2021.170571","article-title":"Potential of plant-derived peptides for the improvement of memory and cognitive function","volume":"142","author":"Katayama","year":"2021","journal-title":"Peptides"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2586","DOI":"10.1021\/jm000077y","article-title":"Enkephalin glycopeptide analogues produce analgesia with reduced dependence liability","volume":"43","author":"Bilsky","year":"2000","journal-title":"J. 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