{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T17:13:41Z","timestamp":1786122821135,"version":"build-2736575974"},"reference-count":38,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T00:00:00Z","timestamp":1786060800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"General Project of Natural Science Research in Jiangsu Province","award":["22KJB180011"],"award-info":[{"award-number":["22KJB180011"]}]},{"name":"Jiangsu Province Double Innovation Doctoral Program","award":["JSSCBS20220478"],"award-info":[{"award-number":["JSSCBS20220478"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The rapid emergence of antimicrobial resistance necessitates the development of novel antimicrobial agents with improved efficacy and selectivity. In this study, a dermatoxin-like peptide, dermatoxin-PD1, was identified from the skin secretion of Pachymedusa dacnicolor, and its structure\u2013activity relationship was investigated through a rational truncation strategy based on predicted proteolytic cleavage sites. A series of truncated analogues was generated, among which a shortened peptide fragment (T1) retained potent antimicrobial activity, particularly against Gram-negative bacteria, whereas further truncation resulted in a marked loss of function. Structural analysis revealed that both dermatoxin-PD1 and T1 adopted amphipathic \u03b1-helical conformations under membrane-mimicking conditions. Functional assays demonstrated that bacterial killing was associated with membrane permeabilisation and depolarisation, with additional evidence supporting interactions with lipopolysaccharide (LPS). Notably, T1 exhibited remarkably reduced haemolytic and cytotoxic effects compared with the parent peptide, resulting in an improved selectivity profile. These findings provide additional insight into the structure\u2013activity relationship of dermatoxin-like peptides and suggest that protease cleavage-guided truncation may represent a useful strategy for developing shorter and safer antimicrobial peptides.<\/jats:p>","DOI":"10.3390\/molecules31162748","type":"journal-article","created":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T11:44:53Z","timestamp":1786103093000},"page":"2748","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification and Structure\u2013Activity Relationship of a Novel Dermatoxin-like Antimicrobial Peptide with Partial LPS-Mediated Membrane Interaction"],"prefix":"10.3390","volume":"31","author":[{"given":"Shiya","family":"Cheng","sequence":"first","affiliation":[{"name":"Natural Drug Discovery Group, School of Pharmacy, Queen\u2019s University Belfast, Belfast BT9 7BL, Northern Ireland, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Zai","sequence":"additional","affiliation":[{"name":"Natural Drug Discovery Group, School of Pharmacy, Queen\u2019s University Belfast, Belfast BT9 7BL, Northern Ireland, UK"},{"name":"School of Life Sciences and Chemical Engineering, Jiangsu Second Normal University, Nanjing 210013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayi","family":"Peng","sequence":"additional","affiliation":[{"name":"Natural Drug Discovery Group, School of Pharmacy, Queen\u2019s University Belfast, Belfast BT9 7BL, Northern Ireland, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3107-9888","authenticated-orcid":false,"given":"Jie","family":"Xiang","sequence":"additional","affiliation":[{"name":"Natural Drug Discovery Group, School of Pharmacy, Queen\u2019s University Belfast, Belfast BT9 7BL, Northern Ireland, UK"},{"name":"School of Traditional Chinese Medicine, Faculty of Medicine, Yangzhou University, Yangzhou 225009, China"},{"name":"Key Laboratory of the Jiangsu Higher Education Institutions for Integrated Traditional Chinese and Western Medicine in Senile Diseases Control, Yangzhou University, Yangzhou 225009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoling","family":"Chen","sequence":"additional","affiliation":[{"name":"Natural Drug Discovery Group, School of Pharmacy, Queen\u2019s University Belfast, Belfast BT9 7BL, Northern Ireland, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengbang","family":"Ma","sequence":"additional","affiliation":[{"name":"Natural Drug Discovery Group, School of Pharmacy, Queen\u2019s University Belfast, Belfast BT9 7BL, Northern Ireland, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5349-8354","authenticated-orcid":false,"given":"Yangyang","family":"Jiang","sequence":"additional","affiliation":[{"name":"Natural Drug Discovery Group, School of Pharmacy, Queen\u2019s University Belfast, Belfast BT9 7BL, Northern Ireland, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3111-2024","authenticated-orcid":false,"given":"Tao","family":"Wang","sequence":"additional","affiliation":[{"name":"Natural Drug Discovery Group, School of Pharmacy, Queen\u2019s University Belfast, Belfast BT9 7BL, Northern Ireland, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8011-9260","authenticated-orcid":false,"given":"Tianbao","family":"Chen","sequence":"additional","affiliation":[{"name":"Natural Drug Discovery Group, School of Pharmacy, Queen\u2019s University Belfast, Belfast BT9 7BL, Northern Ireland, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Shaw","sequence":"additional","affiliation":[{"name":"Natural Drug Discovery Group, School of Pharmacy, Queen\u2019s University Belfast, Belfast BT9 7BL, Northern Ireland, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2576-0252","authenticated-orcid":false,"given":"Mei","family":"Zhou","sequence":"additional","affiliation":[{"name":"Natural Drug Discovery Group, School of Pharmacy, Queen\u2019s University Belfast, Belfast BT9 7BL, Northern Ireland, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8811-8489","authenticated-orcid":false,"given":"Lei","family":"Wang","sequence":"additional","affiliation":[{"name":"Natural Drug Discovery Group, School of Pharmacy, Queen\u2019s University Belfast, Belfast BT9 7BL, Northern Ireland, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Mulani, M.S., Kamble, E.E., Kumkar, S.N., Tawre, M.S., and Pardesi, K.R. 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