{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T21:50:16Z","timestamp":1788558616059,"version":"build-2803163510"},"reference-count":64,"publisher":"Wiley","issue":"21","license":[{"start":{"date-parts":[[2025,3,5]],"date-time":"2025-03-05T00:00:00Z","timestamp":1741132800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100007449","name":"Takeda Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007449","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011313","name":"Tokyo Biochemical Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011313","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chemistry A European J"],"published-print":{"date-parts":[[2025,4,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Medium\u2010sized cyclic peptides are expected to be ideal drug leads because these peptides combine the advantages, while compensating for the disadvantages, of small molecules and antibodies. Although medium\u2010sized peptides can be produced by chemical synthesis, two major problems, namely (i) C\u03b1\u2010epimerization during <jats:italic>C<\/jats:italic>\u2010terminal modification and (ii) side reactions in the cyclization, remain to be solved. These issues have hampered the synthesis of pure materials for bioassays, making it difficult to accomplish accurate structure\u2010activity relationship (SAR) studies. Herein, we report an efficient synthesis of medium\u2010sized cyclic peptides based on the twisted amide\u2010mediated amidation strategy. First, a variety of linear peptides were synthesized by the \u201cinverse\u201d peptide synthesis and fragment coupling. Second, the <jats:italic>C<\/jats:italic>\u2010terminus of the linear peptides were converted to twisted amides, which were then reacted with a variety of \u03b1\u2010amino acyl sulfonamides, realizing the rapid <jats:italic>C<\/jats:italic>\u2010terminal diversification of peptides. Finally, the resulting linear peptides were cyclized by the intramolecular twisted amide\u2010mediated amidation to afford stereochemically pure cyclic peptides. Using this strategy, total synthesis of acyl\u2010surugamide A, the stereoselective synthesis of 13 non\u2010natural analogs, and the discovery of potent antimicrobial\/antifungal peptides beyond the natural product were also achieved.<\/jats:p>","DOI":"10.1002\/chem.202500331","type":"journal-article","created":{"date-parts":[[2025,2,25]],"date-time":"2025-02-25T22:34:44Z","timestamp":1740522884000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Twisted Amide\u2010Mediated Synthesis and Rapid Structure\u2010Activity Relationship Study of Medium\u2010Sized Cyclic Peptides"],"prefix":"10.1002","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2566-2038","authenticated-orcid":false,"given":"Takefumi","family":"Kuranaga","sequence":"first","affiliation":[{"name":"Department of System Chemotherapy and Molecular Sciences Division of Medicinal Frontier Sciences Graduate School of Pharmaceutical Sciences Kyoto University  Yoshida, Sakyo-ku Kyoto 606-8501 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ai","family":"Koyama","sequence":"additional","affiliation":[{"name":"Department of System Chemotherapy and Molecular Sciences Division of Medicinal Frontier Sciences Graduate School of Pharmaceutical Sciences Kyoto University  Yoshida, Sakyo-ku Kyoto 606-8501 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junta","family":"Asano","sequence":"additional","affiliation":[{"name":"Department of System Chemotherapy and Molecular Sciences Division of Medicinal Frontier Sciences Graduate School of Pharmaceutical Sciences Kyoto University  Yoshida, Sakyo-ku Kyoto 606-8501 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takumi","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Department of System Chemotherapy and Molecular Sciences Division of Medicinal Frontier Sciences Graduate School of Pharmaceutical Sciences Kyoto University  Yoshida, Sakyo-ku Kyoto 606-8501 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4293-7331","authenticated-orcid":false,"given":"Hideaki","family":"Kakeya","sequence":"additional","affiliation":[{"name":"Department of System Chemotherapy and Molecular Sciences Division of Medicinal Frontier Sciences Graduate School of Pharmaceutical Sciences Kyoto University  Yoshida, Sakyo-ku Kyoto 606-8501 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,3,5]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-022-00904-4"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.joc.8b03001"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr100048w"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr800323s"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja9637863"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchem.1062"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-3011.1994.tb00393.x"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.8b13178"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202308251"},{"key":"e_1_2_8_10_1","unstructured":"Application to the peptide 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