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Herein, the de\u2009novo design of transmembrane ion channels made up of amphiphilic peptide\u2013oligourea chimeric helices is described. They consist of an oligourea segment (7\u2010mer) attached to the C\u2010terminus of a short peptide (8\u2010mer). Mass spectrometry (MS) and transmission electron microscopy (TEM) analyses show that in an aqueous solution, two of these chimeras (HPU\u2010E and HPU\u2010N) independently form defined oligomeric structures. TEM also shows that they form fiber bundles. The third related chimera HPU\u2010F does not oligomerize (MS) but forms spherical nanostructures (TEM). HPU\u2010E and HPU\u2010N exhibit anion transport activity across lipid bilayers via antiport mechanism (HPU\u2010N\u2009&gt;\u2009HPU\u2010E). The anion selectivity of HPU\u2010N is Cl<jats:sup>\u2212<\/jats:sup>&gt;NO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup>\u2009&gt;\u2009Br<jats:sup>\u2212<\/jats:sup>&gt;SCN<jats:sup>\u2212<\/jats:sup>\u2009&gt;\u2009I<jats:sup>\u2212<\/jats:sup>\u2009&gt;\u2009AcO<jats:sup>\u2212<\/jats:sup>&gt;F<jats:sup>\u2212<\/jats:sup>, which can be due to anion binding within the channels rather than size exclusion. Patch\u2010clamp data support HPU\u2010N's Cl<jats:sup>\u2212<\/jats:sup> selectivity (PCl<jats:sup>\u2212<\/jats:sup>\/PI<jats:sup>\u2212<\/jats:sup>\u2009=\u20093.26). X\u2010ray crystal structure (1.77\u2009\u00c5) of HPU\u2010N reveals well\u2010packed \u03b1\u2010helices, and cryo\u2010electron microscopy data shows the formation of nanotubes (13.7\u2009\u00c5 diameter pores) and transmembrane channels. The study shows that \u03b1\u2010peptide\u2013oligourea\u2010based de\u2009novo design can yield unique bioactive molecules with defined structures and functions.<\/jats:p>","DOI":"10.1002\/smsc.202300352","type":"journal-article","created":{"date-parts":[[2024,5,31]],"date-time":"2024-05-31T06:44:37Z","timestamp":1717137877000},"source":"Crossref","is-referenced-by-count":8,"title":["Innovative Self\u2010Assembly of 15\u2010Mer Chimeric \u03b1\u2010Peptide\u2013Oligourea Foldamers toward Cl<sup>\u2212<\/sup>\u2010Selective Ion Channels"],"prefix":"10.1002","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4206-207X","authenticated-orcid":false,"given":"Chiranjit","family":"Dutta","sequence":"first","affiliation":[{"name":"Department of Biological Sciences National University of Singapore  Singapore 117543 Singapore"},{"name":"NUS Environmental Research Institute (NERI) National University of Singapore  Singapore 117411 Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pannaga","family":"Krishnamurthy","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences National University of Singapore  Singapore 117543 Singapore"},{"name":"NUS Environmental Research Institute (NERI) National University of Singapore  Singapore 117411 Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dandan","family":"Su","sequence":"additional","affiliation":[{"name":"Institut Europ\u00e9en des Membranes Adaptive Supramolecular Nanosystems Group University of Montpellier ENSCM, CNRS  Place Eug\u00e8ne Bataillon, CC 047 F\u201034095 Montpellier France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianwei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences National University of Singapore  Singapore 117543 Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9247-0434","authenticated-orcid":false,"given":"Sung Hyun","family":"Yoo","sequence":"additional","affiliation":[{"name":"Institut Europ\u00e9en de Chimie et Biologie Univ. 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