{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T12:42:35Z","timestamp":1791031355768,"version":"4.1.0"},"reference-count":52,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2009,1,1]],"date-time":"2009-01-01T00:00:00Z","timestamp":1230768000000},"content-version":"vor","delay-in-days":1767,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Protein Science"],"published-print":{"date-parts":[[2004,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Antimicrobial peptides are key components of the innate immune response in most multicellular organisms. These molecules are considered as one of the most innovative class of anti\u2010infective agents that have been discovered over the last two decades, and therefore, as a source of inspiration for novel drug design. Insect cystein\u2010rich antimicrobial peptides with the CS\u03b1\u03b2 scaffold (an \u03b1\u2010helix linked to a \u03b2\u2010sheet by two disulfide bridges) represent particularly attractive templates for the development of systemic agents owing to their remarkable resistance to protease degradation. We have selected heliomicin, a broad spectrum antifungal CS\u03b1\u03b2 peptide from Lepidoptera as the starting point of a lead optimization program based on phylogenic exploration and fine tuned mutagenesis. We report here the characterization, biological activity, and 3D structure of heliomicin improved analogs, namely the peptides ARD1, ETD\u2010135, and ETD\u2010151. The ARD1 peptide was initially purified from the immune hemolymph of the caterpillars of <jats:italic>Archeoprepona demophoon<\/jats:italic>. Although it differs from heliomicin by only two residues, it was found to be more active against the human pathogens <jats:italic>Aspergillus fumigatus<\/jats:italic> and <jats:italic>Candida albicans<\/jats:italic>. The peptides ETD\u2010135 and ETD\u2010151 were engineered by site\u2010directed mutagenesis of ARD1 in either cationic or hydrophobic regions. ETD\u2010135 and ETD\u2010151 demonstrated an improved antifungal activity over the native peptides, heliomicin and ARD1. A comparative analysis of the 3D structure of the four molecules highlighted the direct impact of the modification of the amphipathic properties on the molecule potency. In addition, it allowed to characterize an optimal organization of cationic and hydrophobic regions to achieve best antifungal activity.<\/jats:p>","DOI":"10.1110\/ps.03404404","type":"journal-article","created":{"date-parts":[[2004,2,21]],"date-time":"2004-02-21T02:22:57Z","timestamp":1077330177000},"page":"703-713","source":"Crossref","is-referenced-by-count":44,"title":["Lead optimization of antifungal peptides with 3D NMR structures analysis"],"prefix":"10.1002","volume":"13","author":[{"given":"C\u00e9line","family":"Landon","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florent","family":"Barbault","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mich\u00e8le","family":"Legrain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laure","family":"Menin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Guenneugues","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val\u00e9rie","family":"Schott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7oise","family":"Vovelle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Luc","family":"Dimarcq","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,1]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1996.0575p.x"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-9452(02)00053-5"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1720574"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/70705"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444998003254"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1992.tb17371.x"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0145-305X(99)00015-4"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nsb0698-427"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1993.1778"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0969-2126(01)00177-0"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1110\/ps.0228303"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00197809"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.43.1.1"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.2.1171"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0282(1998)47:6<465::AID-BIP5>3.0.CO;2-#"},{"key":"e_1_2_8_17_1","unstructured":"Dixon D.M.andEdwards J.E.2000.Summary draft report of the antifungal working group. 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