{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:28:49Z","timestamp":1787016529733,"version":"build-2736575974"},"reference-count":48,"publisher":"American Society for Microbiology","issue":"6","license":[{"start":{"date-parts":[[2012,6,1]],"date-time":"2012-06-01T00:00:00Z","timestamp":1338508800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2012,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Antimicrobial peptides (AMPs) have therapeutic potential, particularly for localized infections such as those of the lung. Here we show that airway administration of a pegylated AMP minimizes lung tissue toxicity while nevertheless maintaining antimicrobial activity. CaLL, a potent synthetic AMP (KWKLFKKIFKRIVQRIKDFLR) comprising fragments of LL-37 and cecropin A peptides, was N-terminally pegylated (PEG-CaLL). PEG-CaLL derivatives retained significant antimicrobial activity (50% inhibitory concentrations [IC\n                    <jats:sub>50<\/jats:sub>\n                    s] 2- to 3-fold higher than those of CaLL) against bacterial lung pathogens even in the presence of lung lining fluid. Circular dichroism and fluorescence spectroscopy confirmed that conformational changes associated with the binding of CaLL to model microbial membranes were not disrupted by pegylation. Pegylation of CaLL reduced AMP-elicited cell toxicity as measured using\n                    <jats:italic>in vitro<\/jats:italic>\n                    lung epithelial primary cell cultures. Further, in a fully intact\n                    <jats:italic>ex vivo<\/jats:italic>\n                    isolated perfused rat lung (IPRL) model, airway-administered PEG-CaLL did not result in disruption of the pulmonary epithelial barrier, whereas CaLL caused an immediate loss of membrane integrity leading to pulmonary edema. All AMPs (CaLL, PEG-CaLL, LL-37, cecropin A) delivered to the lung by airway administration showed limited (&lt;3%) pulmonary absorption in the IPRL with extensive AMP accumulation in lung tissue itself, a characteristic anticipated to be beneficial for the treatment of pulmonary infections. We conclude that pegylation may present a means of improving the lung biocompatibility of AMPs designed for the treatment of pulmonary infections.\n                  <\/jats:p>","DOI":"10.1128\/aac.06335-11","type":"journal-article","created":{"date-parts":[[2012,3,19]],"date-time":"2012-03-19T23:32:13Z","timestamp":1332199933000},"page":"3298-3308","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":85,"title":["Pegylation of Antimicrobial Peptides Maintains the Active Peptide Conformation, Model Membrane Interactions, and Antimicrobial Activity while Improving Lung Tissue Biocompatibility following Airway Delivery"],"prefix":"10.1128","volume":"56","author":[{"given":"Christopher J.","family":"Morris","sequence":"first","affiliation":[{"name":"School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konrad","family":"Beck","sequence":"additional","affiliation":[{"name":"School of Dentistry, Cardiff University, Cardiff, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc A.","family":"Fox","sequence":"additional","affiliation":[{"name":"Biomedical Sciences, Defence Science and Technology Laboratory, Porton Down, Salisbury, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Ulaeto","sequence":"additional","affiliation":[{"name":"Biomedical Sciences, Defence Science and Technology Laboratory, Porton Down, Salisbury, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graeme C.","family":"Clark","sequence":"additional","affiliation":[{"name":"Biomedical Sciences, Defence Science and Technology Laboratory, Porton Down, Salisbury, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Gumbleton","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1039\/b904878b","article-title":"Systemic in vivo distribution of activatable cell penetrating peptides is superior to that of cell penetrating peptides","volume":"1","author":"Aguilera TA","year":"2009","unstructured":"AguileraTA OlsonES TimmersMM JiangT TsienRY. 2009. 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