{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T23:49:08Z","timestamp":1773877748060,"version":"3.50.1"},"reference-count":55,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2023,9,23]],"date-time":"2023-09-23T00:00:00Z","timestamp":1695427200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Antimicrobial peptides have gradually attracted interest as promising alternatives to conventional agents to control the worldwide health threats posed by antibiotic resistance and cancer. Crabrolin is a tridecapeptide extracted from the venom of the European hornet (Vespa crabro). Its antibacterial and anticancer potentials have been underrated compared to other peptides discovered from natural resources. Herein, a series of analogs were designed based on the template sequence of crabrolin to study its structure\u2013activity relationship and enhance the drug\u2019s potential by changing the number, type, and distribution of charged residues. The cationicity-enhanced derivatives were shown to have improved antibacterial and anticancer activities with a lower toxicity. Notably, the double-arginine-modified product, crabrolin-TR, possessed a potent capacity against Pseudomonas aeruginosa (minimum inhibitory concentration (MIC) = 4 \u03bcM), which was around thirty times stronger than the parent peptide (MIC = 128 \u03bcM). Furthermore, crabrolin-TR showed an in vivo treatment efficacy in a Klebsiella-pneumoniae-infected waxworm model and was non-toxic under its maximum MBC value (MIC = 8 \u03bcM), indicating its therapeutic potency and better selectivity. Overall, we rationally designed functional peptides by progressively increasing the number and distribution of charged residues, demonstrating new insights for developing therapeutic molecules from natural resources with enhanced properties, and proposed crabrolin-TR as an appealing antibacterial and anticancer agent candidate for development.<\/jats:p>","DOI":"10.3390\/ijms241914472","type":"journal-article","created":{"date-parts":[[2023,9,24]],"date-time":"2023-09-24T10:36:26Z","timestamp":1695551786000},"page":"14472","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["A Designed Analog of an Antimicrobial Peptide, Crabrolin, Exhibits Enhanced Anti-Proliferative and In Vivo Antimicrobial Activity"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8676-2000","authenticated-orcid":false,"given":"Aifang","family":"Yao","sequence":"first","affiliation":[{"name":"College of Biological Science and Engineering, Fuzhou University, Fuzhou 350108, China"},{"name":"School of Pharmacy, Queen\u2019s University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yingxue","family":"Ma","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Queen\u2019s University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruize","family":"Sun","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Queen\u2019s University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wanchen","family":"Zou","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Queen\u2019s University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoling","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Queen\u2019s University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2576-0252","authenticated-orcid":false,"given":"Mei","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Queen\u2019s University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chengbang","family":"Ma","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Queen\u2019s University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8011-9260","authenticated-orcid":false,"given":"Tianbao","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Queen\u2019s University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chris","family":"Shaw","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Queen\u2019s University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8811-8489","authenticated-orcid":false,"given":"Lei","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Queen\u2019s University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,23]]},"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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