{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T14:58:14Z","timestamp":1790693894940,"version":"4.1.0"},"reference-count":33,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2015,7,6]],"date-time":"2015-07-06T00:00:00Z","timestamp":1436140800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2015,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Peptide dendrimers are a class of molecules of high interest in the search for new antibiotics. We used microwave\u2010assisted, copper(I)\u2010catalyzed alkyne\u2013azide cycloaddition (CuAAC; \u201cclick\u201d chemistry) for the simple and versatile synthesis of a new class of multivalent antimicrobial peptides (AMPs) containing solely arginine and tryptophan residues. To investigate the influence of multivalency on antibacterial activity, short solid\u2010phase\u2010 synthesized azide\u2010modified Arg\u2010Trp\u2010containing peptides were \u201cclicked\u201d to three different alkyne\u2010modified benzene scaffolds to access scaffolds with one, two, or three peptides. The antibacterial activity of 15 new AMPs was investigated by minimal inhibitory concentration (MIC) assays on five different bacterial strains, including a multidrug\u2010resistant <jats:italic>Staphylococcus aureus<\/jats:italic> (MRSA) strain. With ultrashort (2\u20133 residues) peptides, a clear synergistic effect of the trivalent display was observed, whereas this effect was not apparent with longer peptides. The best candidates showed activities in the low\u2010micromolar range against Gram\u2010positive MRSA. Surprisingly, the best activity against Gram\u2010negative <jats:italic>Acinetobacter baumannii<\/jats:italic> was observed with an ultrashort dipeptide on the trivalent scaffold (MIC: 7.5\u2005\u03bc<jats:sc>M<\/jats:sc>). The hemolytic activity was explored for the three most active peptides. At concentrations ten times the MIC values, &lt;1\u2009% hemolysis of red blood cells was observed.<\/jats:p>","DOI":"10.1002\/cmdc.201500220","type":"journal-article","created":{"date-parts":[[2015,7,6]],"date-time":"2015-07-06T14:48:17Z","timestamp":1436194097000},"page":"1564-1569","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Influence of the Multivalency of Ultrashort Arg\u2010Trp\u2010Based Antimicrobial Peptides (AMP) on Their Antibacterial Activity"],"prefix":"10.1002","volume":"10","author":[{"given":"Barbara C.","family":"Hoffknecht","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis J.","family":"Worm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Bobersky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal","family":"Prochnow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia E.","family":"Bandow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nils","family":"Metzler\u2010Nolte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,7,6]]},"reference":[{"key":"e_1_2_6_1_2","unstructured":"World Health Organization Antimicrobial Resistance: Global Report on Surveillance 2014; ISBN: 978 924 156 4748 www.who.int\/drugresistance\/documents\/surveillancereport\/en\/."},{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10989-010-9230-z"},{"key":"e_1_2_6_3_2","unstructured":"\u00a0"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/415389a"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-7799(97)01156-6"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1021\/cb1001558"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1267"},{"key":"e_1_2_6_8_2","unstructured":"\u00a0"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.3762\/bjoc.8.200"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jorganchem.2005.07.007"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.200600117"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1039\/C4SC01822B"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1319900111"},{"key":"e_1_2_6_14_2","unstructured":"\u00a0"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi962507l"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1021\/co400072q"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1021\/ml300148v"},{"key":"e_1_2_6_18_2","unstructured":"\u00a0"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/psc.365"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/psc.398"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm0340039"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2012.04.004"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1039\/b904091a"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/1521-3773(20010601)40:11<2004::AID-ANIE2004>3.0.CO;2-5"},{"key":"e_1_2_6_24_3","doi-asserted-by":"publisher","DOI":"10.1002\/1521-3757(20010601)113:11<2056::AID-ANGE2056>3.0.CO;2-W"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1021\/ol701581g"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.3961484"},{"key":"e_1_2_6_27_2","unstructured":"\u00a0"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.15227\/orgsyn.065.0108"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1021\/ol034534r"},{"key":"e_1_2_6_30_2","doi-asserted-by":"publisher","DOI":"10.15227\/orgsyn.088.0238"},{"key":"e_1_2_6_31_2","volume-title":"Mosby's Medical Dictionary","year":"2009"},{"key":"e_1_2_6_32_2","doi-asserted-by":"publisher","DOI":"10.1039\/C4MD00327F"}],"container-title":["ChemMedChem"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcmdc.201500220","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cmdc.201500220","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T10:33:28Z","timestamp":1760265208000},"score":1,"resource":{"primary":{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/10.1002\/cmdc.201500220"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,7,6]]},"references-count":33,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2015,9]]}},"alternative-id":["10.1002\/cmdc.201500220"],"URL":"https:\/\/doi.org\/10.1002\/cmdc.201500220","archive":["Portico"],"relation":{},"ISSN":["1860-7179","1860-7187"],"issn-type":[{"value":"1860-7179","type":"print"},{"value":"1860-7187","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,7,6]]},"assertion":[{"value":"2015-05-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-07-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}