{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T05:19:10Z","timestamp":1788153550149,"version":"build-2803163510"},"reference-count":40,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T00:00:00Z","timestamp":1788048000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program","doi-asserted-by":"publisher","award":["2024YFD2401903"],"award-info":[{"award-number":["2024YFD2401903"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"name":"China Agriculture Research System","award":["CARS-49"],"award-info":[{"award-number":["CARS-49"]}]},{"award":["CARS-49"],"award-info":[{"award-number":["CARS-49"]}],"id":[{"id":"https:\/\/ror.org\/03p5eky76","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Guangdong Province Modern Agricultural Industry Technology System Innovation Team Construction Project","award":["2024CXTD23"],"award-info":[{"award-number":["2024CXTD23"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Mar. Drugs","Marine Drugs"],"abstract":"<jats:p>Excessive melanin accumulation induced by UV exposure and hormonal changes poses significant challenges to skin health, necessitating safe and effective tyrosinase inhibitors. Pearl and nacre powder have long been utilized in traditional Chinese medicine for skin whitening. Our previous study identified a tyrosinase inhibitory peptide (Ala-His-Tyr-Tyr-Asp) from Pinctada martensii nacre in silico; however, chemical modification strategies for enhancing bioactive peptide efficacy remain underexplored. The present study investigated the structure-activity relationship of NP-TIP-1 (Tyrosinase Inhibitory Peptide of Nacre Powder-1) through three chemical modifications (C-terminal amidation, N-terminal acetylation, and N-terminal palmitoylation). C-terminal amidation significantly improved tyrosinase inhibitory potency, reducing the IC50 value from 2.012 \u00b1 0.088 mM to 0.979 \u00b1 0.028 mM, while retaining thermal stability and copper ion chelating capacity comparable to the native peptide. In B16F10 melanoma cells, NP-TIP-1-NH2 (C-terminally amidated NP-TIP-1) exhibited no cytotoxicity at concentrations up to 600 \u03bcM and concentration-dependently suppressed intracellular tyrosinase activity and melanin content. Mechanistic investigation revealed that NP-TIP-1-NH2 treatment downregulates the mRNA and protein expression of TYR and TRP-1 without affecting MITF (Microphthalmia-associated Transcription Factor) or TRP-2, suggesting a potential regulatory mechanism independent of MITF-mediated transcriptional control. Non-targeted metabolomics further identified nucleotide metabolism, purine metabolism, and glycine\/serine\/threonine metabolism as the most significantly perturbed pathways, with cytosine and GMP downregulated while guanosine and guanine were upregulated. This study establishes NP-TIP-1-NH2 as a promising candidate for multifunctional food preservatives and nutraceuticals, providing a strategic framework for C-terminal amidation as a structure-activity optimization approach for marine-derived anti-melanogenic peptides.<\/jats:p>","DOI":"10.3390\/md24090303","type":"journal-article","created":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T04:24:03Z","timestamp":1788150243000},"page":"303","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Enhancement of Anti-Melanogenic Activity of Pinctada martensii Nacre-Derived Peptide Through C-Terminal Amidation: Mechanism Investigation in B16F10 Cells"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9823-2584","authenticated-orcid":false,"given":"Haisheng","family":"Lin","sequence":"first","affiliation":[{"name":"National Research and Development Branch Center for Shellfish Processing (Zhanjiang), Guangdong Provincial Key Laboratory of Aquatic Products Processing and Safety, Guangdong Provincial Engineering Technology Research Center of Seafood, Guangdong Province Engineering Laboratory for Marine Biological Products, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]},{"given":"Ruonan","family":"Chang","sequence":"additional","affiliation":[{"name":"National Research and Development Branch Center for Shellfish Processing (Zhanjiang), Guangdong Provincial Key Laboratory of Aquatic Products Processing and Safety, Guangdong Provincial Engineering Technology Research Center of Seafood, Guangdong Province Engineering Laboratory for Marine Biological Products, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Fei","family":"Li","sequence":"additional","affiliation":[{"name":"National Research and Development Branch Center for Shellfish Processing (Zhanjiang), Guangdong Provincial Key Laboratory of Aquatic Products Processing and Safety, Guangdong Provincial Engineering Technology Research Center of Seafood, Guangdong Province Engineering Laboratory for Marine Biological Products, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, 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China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2249-7092","authenticated-orcid":false,"given":"Zhongqin","family":"Chen","sequence":"additional","affiliation":[{"name":"National Research and Development Branch Center for Shellfish Processing (Zhanjiang), Guangdong Provincial Key Laboratory of Aquatic Products Processing and Safety, Guangdong Provincial Engineering Technology Research Center of Seafood, Guangdong Province Engineering Laboratory for Marine Biological Products, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8308-7759","authenticated-orcid":false,"given":"Yuanwei","family":"Liang","sequence":"additional","affiliation":[{"name":"College of Chemistry and Environmental Science, Guangdong Ocean University, Zhanjiang 524088, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]},{"given":"Wenhong","family":"Cao","sequence":"additional","affiliation":[{"name":"National Research and Development Branch Center for Shellfish Processing (Zhanjiang), Guangdong Provincial Key Laboratory of Aquatic Products Processing and Safety, Guangdong Provincial Engineering Technology Research Center of Seafood, Guangdong Province Engineering Laboratory for Marine Biological Products, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China"},{"name":"Shenzhen Institute of Guangdong Ocean University, Shenzhen 518108, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]},{"given":"Huina","family":"Zheng","sequence":"additional","affiliation":[{"name":"National Research and Development Branch Center for Shellfish Processing (Zhanjiang), Guangdong Provincial Key Laboratory of Aquatic Products Processing and Safety, Guangdong Provincial Engineering Technology Research Center of Seafood, Guangdong Province Engineering Laboratory for Marine Biological Products, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang 524088, China"},{"name":"Shenzhen Institute of Guangdong Ocean University, Shenzhen 518108, 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