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We previously developed a modified antigen-specific peptide, m-P14, derived from the nephritogenic epitope \u03b13127\u2013148, which ameliorated experimental anti-GBM nephritis. However, its short half-life limits clinical translation. This study evaluated a butyrate-conjugated derivative (m-P14-BA) to improve pharmacokinetic properties while preserving therapeutic efficacy. M-P14-BA and m-P14 were administered to \u03b13127\u2013148 immunized Wistar Kyoto rats in early and late treatment settings. Renal injury parameters and intrarenal inflammation were assessed, and pharmacokinetic profiles were evaluated following intraperitoneal administration in beagle dogs. M-P14-BA reduced proteinuria, crescent formation, glomerular IgG deposition, complement activation, and inflammatory cell infiltration, with overall efficacy comparable to m-P14 in early treatment settings. In late treatment settings, m-P14-BA was associated with a significant improvement in blood urea nitrogen levels and modest reductions in proteinuria and histopathological injury. Butyrate conjugation markedly improved pharmacokinetics, prolonging plasma elimination half-life by approximately 2.8-fold and increasing systemic exposure nearly fourfold. These pharmacokinetic improvements were associated with maintained therapeutic efficacy at a reduced dose, with 10 mg\/kg m-P14-BA achieving effects broadly similar to those observed with 30 mg\/kg m-P14. In summary, butyrate conjugation improves the pharmacokinetic profile of an antigen-specific therapeutic peptide while preserving therapeutic activity, suggesting a potential strategy to enhance the translational feasibility of peptide-based immunotherapy in anti-GBM disease.<\/jats:p>","DOI":"10.3390\/ijms27114810","type":"journal-article","created":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T12:31:56Z","timestamp":1779885116000},"page":"4810","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Butyric Acid-Modified m-P14 Peptide Ameliorates Anti-Glomerular Basement Membrane Disease"],"prefix":"10.3390","volume":"27","author":[{"given":"Nan","family":"Jiang","sequence":"first","affiliation":[{"name":"Renal Division, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, Beijing 100034, China"},{"name":"Institute of Nephrology, Peking University, Beijing 100034, China"},{"name":"Key Laboratory of Renal Disease, Ministry of Health of China, Beijing 100034, China"},{"name":"Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Ministry of Education of China, Beijing 100034, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan-Lun","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, Beijing 100034, China"},{"name":"State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Xue Yuan Rd. 38, Haidian District, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7739-291X","authenticated-orcid":false,"given":"Huang","family":"Kuang","sequence":"additional","affiliation":[{"name":"Renal Division, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, Beijing 100034, China"},{"name":"Institute of Nephrology, Peking University, Beijing 100034, China"},{"name":"Key Laboratory of Renal Disease, Ministry of Health of China, Beijing 100034, China"},{"name":"Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Ministry of Education of China, Beijing 100034, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhao","family":"Cui","sequence":"additional","affiliation":[{"name":"Renal Division, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, Beijing 100034, China"},{"name":"Institute of Nephrology, Peking University, Beijing 100034, China"},{"name":"Key Laboratory of Renal Disease, Ministry of Health of China, Beijing 100034, China"},{"name":"Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Ministry of Education of China, Beijing 100034, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3340-3108","authenticated-orcid":false,"given":"Ming-Hui","family":"Zhao","sequence":"additional","affiliation":[{"name":"Renal Division, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, Beijing 100034, China"},{"name":"Institute of Nephrology, Peking University, Beijing 100034, China"},{"name":"Key Laboratory of Renal Disease, Ministry of Health of China, Beijing 100034, China"},{"name":"Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Ministry of Education of China, Beijing 100034, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Cong","family":"Pang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, Beijing 100034, China"},{"name":"State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Xue Yuan Rd. 38, Haidian District, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Yu","family":"Jia","sequence":"additional","affiliation":[{"name":"Renal Division, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, Beijing 100034, China"},{"name":"Institute of Nephrology, Peking University, Beijing 100034, China"},{"name":"Key Laboratory of Renal Disease, Ministry of Health of China, Beijing 100034, China"},{"name":"Key Laboratory of Chronic Kidney Disease Prevention and Treatment, Ministry of Education of China, Beijing 100034, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1038\/nrneph.2011.89","article-title":"Advances in human antiglomerular basement membrane disease","volume":"7","author":"Cui","year":"2011","journal-title":"Nat. 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