{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T05:54:45Z","timestamp":1791438885463,"version":"4.3.3"},"reference-count":110,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2026,8,14]]},"abstract":"<jats:p>\n                    Temporins A\u2013L, a family of short antimicrobial peptides isolated from the skin secretions of\n                    <jats:italic>Rana temporaria<\/jats:italic>\n                    , have emerged as promising scaffolds for the development of novel anti\u2010infective agents. However, their therapeutic translation is limited by issues such as modest selectivity, susceptibility to proteolytic degradation, and variable potency. In this review, we provide an overview of the medicinal chemistry efforts devoted to the optimization of this class of AMPs through systematic chemical modifications. Strategies including backbone alterations (e.g., D\u2010amino acid incorporation and retro\u2010inverso design), side chain modulation, charge tuning, hydrophobicity adjustment, and the introduction of noncanonical residues are discussed in relation to their impact on antimicrobial activity and selectivity. Particular attention is given to conformationally constrained analogs, such as cyclic, stapled, and bicyclic derivatives, which often display enhanced stability and bioactivity. By integrating available data, we delineated key structure\u2013activity relationships governing temporin function and identified emerging design principles for the development of improved analogs. Finally, current challenges and future perspectives for the advancement of temporin\u2010based therapeutics in medicinal chemistry are outlined.\n                  <\/jats:p>","DOI":"10.1002\/cmdc.70397","type":"journal-article","created":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T01:09:55Z","timestamp":1785546595000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Chemical Optimization of Temporin A\u2013L Peptides: From Native Isoforms to Enhanced Antimicrobial Analogs"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-6662-007X","authenticated-orcid":false,"given":"Ida","family":"Boccino","sequence":"first","affiliation":[{"name":"Department of Pharmacy University of Naples Federico II  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6854-8123","authenticated-orcid":false,"given":"Paolo","family":"Grieco","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Naples Federico II  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9607-229X","authenticated-orcid":false,"given":"Francesco","family":"Merlino","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Naples Federico II  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,31]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/frabi.2022.984076"},{"key":"e_1_2_9_3_1","unstructured":"World Health Organization \u201cTen Threats to Global Health in 2019 \u201d accessed July 16 2026 can be found underhttps:\/\/www.who.int\/news\u2010room\/spotlight\/ten\u2010threats\u2010to\u2010global\u2010health\u2010in\u20102019 2019."},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41570-021-00313-1"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.2174\/092986733001221104121552"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1155\/2023\/5250040"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.1c10200"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)02724-0"},{"key":"e_1_2_9_9_1","unstructured":"BioMed Research International \u201cAntibacterial products in preclinical development for bacterial priority pathogens \u201d accessed July 16 2026 can be found underhttps:\/\/www.who.int\/publications\/i\/item\/9789240113091 2025."},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(15)00466-1"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-019-0288-0"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(20)30327-3"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-019-0058-8"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-021-00585-w"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd3591"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1039\/D0CS00729C"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep35465"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2010.07.003"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.43.6.1317"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.3390\/fermentation10110540"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/jam.15314"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(01)00092-5"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1101130108"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1080\/20477724.2016.1195036"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2006.07.001"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics3040461"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222111401"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom8010004"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.130955"},{"key":"e_1_2_9_30_1","first-page":"275","volume-title":"Biomedical Engineering, Trends, Research and Technologies","author":"L\u00f3pez\u2010Meza J. 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