{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T01:19:43Z","timestamp":1789521583583,"version":"build-2803163510"},"reference-count":36,"publisher":"Wiley","issue":"31","license":[{"start":{"date-parts":[[2024,6,26]],"date-time":"2024-06-26T00:00:00Z","timestamp":1719360000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP23H04909 and JP23H05466"],"award-info":[{"award-number":["JP23H04909 and JP23H05466"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP20H05843"],"award-info":[{"award-number":["JP20H05843"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP23H04911"],"award-info":[{"award-number":["JP23H04911"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001695","name":"Japan Science and Technology Corporation","doi-asserted-by":"publisher","award":["JPMJPR21C9"],"award-info":[{"award-number":["JPMJPR21C9"]}],"id":[{"id":"10.13039\/501100001695","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Angew Chem Int Ed"],"published-print":{"date-parts":[[2024,7,29]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Pathogenic protein aggregates, called amyloids, are etiologically relevant to various diseases, including neurodegenerative Alzheimer disease. Catalytic photooxygenation of amyloids, such as amyloid\u2010\u03b2 (A\u03b2), reduces their toxicity; however, the requirement for light irradiation may limit its utility in large animals, including humans, due to the low tissue permeability of light. Here, we report that <jats:italic>Cypridina<\/jats:italic> luciferin analogs, <jats:bold>dmCLA\u2010Cl<\/jats:bold> and <jats:bold>dmCLA\u2010Br<\/jats:bold>, promoted selective oxygenation of amyloids through chemiexcitation without external light irradiation. Further structural optimization of <jats:bold>dmCLA\u2010Cl<\/jats:bold> led to the identification of a derivative with a polar carboxylate functional group and low cellular toxicity: <jats:bold>dmCLA\u2010Cl\u2010acid<\/jats:bold>. <jats:bold>dmCLA\u2010Cl\u2010acid<\/jats:bold> promoted oxygenation of A\u03b2 amyloid and reduced its cellular toxicity without photoirradiation. The chemiexcited oxygenation developed in this study may be an effective approach to neutralizing the toxicity of amyloids, which can accumulate deep inside the body, and treating amyloidosis.<\/jats:p>","DOI":"10.1002\/anie.202405605","type":"journal-article","created":{"date-parts":[[2024,5,17]],"date-time":"2024-05-17T07:49:05Z","timestamp":1715932145000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Unimolecular Chemiexcited Oxygenation of Pathogenic Amyloids"],"prefix":"10.1002","volume":"63","author":[{"given":"Hiroki","family":"Umeda","sequence":"first","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences The University of Tokyo  Tokyo 113-0033 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kayo","family":"Suda","sequence":"additional","affiliation":[{"name":"Graduate School of Arts and Sciences The University of Tokyo  Tokyo 153-8902 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Yokogawa","sequence":"additional","affiliation":[{"name":"Graduate School of Arts and Sciences The University of Tokyo  Tokyo 153-8902 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuto","family":"Azumaya","sequence":"additional","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences The University of Tokyo  Tokyo 113-0033 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuo","family":"Kitada","sequence":"additional","affiliation":[{"name":"Graduate School of Informatics and Engineering The University of Electro-Communications, Chofu  Tokyo 182-8585 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shojiro A.","family":"Maki","sequence":"additional","affiliation":[{"name":"Graduate School of Informatics and Engineering The University of Electro-Communications, Chofu  Tokyo 182-8585 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigehiro A.","family":"Kawashima","sequence":"additional","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences The University of Tokyo  Tokyo 113-0033 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harunobu","family":"Mitsunuma","sequence":"additional","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences The University of Tokyo  Tokyo 113-0033 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Yamanashi","sequence":"additional","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences The University of Tokyo  Tokyo 113-0033 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1977-7648","authenticated-orcid":false,"given":"Motomu","family":"Kanai","sequence":"additional","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences The University of Tokyo  Tokyo 113-0033 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,6,26]]},"reference":[{"key":"e_1_2_3_1_1","unstructured":"\u00a0"},{"key":"e_1_2_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-018-0060-8"},{"key":"e_1_2_3_3_2","doi-asserted-by":"publisher","DOI":"10.1039\/C9CS00199A"},{"key":"e_1_2_3_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2212948"},{"key":"e_1_2_3_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tet.2022.133227"},{"key":"e_1_2_3_6_1","doi-asserted-by":"publisher","DOI":"10.1039\/D1OB01677F"},{"key":"e_1_2_3_7_1","unstructured":"For representative chemical modifications of amyloids other than photooxygenation See:"},{"key":"e_1_2_3_8_2","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.6b09681"},{"key":"e_1_2_3_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1916944117"},{"key":"e_1_2_3_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202115336"},{"key":"e_1_2_3_11_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abc9750"},{"key":"e_1_2_3_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/lsm.22343"},{"key":"e_1_2_3_13_1","unstructured":"\u00a0"},{"key":"e_1_2_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-17783-4"},{"key":"e_1_2_3_15_2","volume":"120","author":"Zhang J.","year":"2023","journal-title":"Proc. Nat. Acad. Sci."},{"key":"e_1_2_3_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202314468"},{"key":"e_1_2_3_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202312519"},{"key":"e_1_2_3_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2019.111683"},{"key":"e_1_2_3_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awab058"},{"key":"e_1_2_3_20_1","doi-asserted-by":"publisher","DOI":"10.1039\/b713374j"},{"key":"e_1_2_3_21_1","doi-asserted-by":"publisher","DOI":"10.1021\/ar300053p"},{"key":"e_1_2_3_22_1","doi-asserted-by":"publisher","DOI":"10.1039\/D1CS00239B"},{"key":"e_1_2_3_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/psc.649"},{"key":"e_1_2_3_24_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacsau.2c00281"},{"key":"e_1_2_3_25_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsomega.8b00286"},{"key":"e_1_2_3_26_1","doi-asserted-by":"publisher","DOI":"10.1070\/PU2005v048n03ABEH001761"},{"key":"e_1_2_3_27_1","unstructured":"We synthesizeddmCLA-Iand evaluated its luminescence properties (Figures\u2005S9\u2013S10 and Table\u2005S1) and oxygenation activity (Figures\u2005S12 and S18).dmCLA-Ifurnished smaller oxygenation activity thandmCLA-ClanddmCLA-Br.ADLumin-1\u2009and ADLumin-1-Clwere also less reactive thandmCLA-ClanddmCLA-Br(Figure\u2005S13)."},{"key":"e_1_2_3_28_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C200338200"},{"key":"e_1_2_3_29_1","unstructured":"Direct chemiexcitation to the triplet excited state through the decarboxylation process might also be operating and this pathway could attribute to the off-target activity. The amyloid-selective oxygenation proceeded with S1(dmAmide-X) which was generated by photoexcitation ofdmAmide-X(Figure\u2005S19)."},{"key":"e_1_2_3_30_1","unstructured":"The conversion rate ofdmCLA-CltodmAmide-Clwas identical in the presence or absence of aggregated A\u03b2 or NKA suggesting that the substrate binding does not affect the chemiluminescence step (Figure\u2005S20)."},{"key":"e_1_2_3_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00726-019-02787-2"},{"key":"e_1_2_3_32_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.0c09926"},{"key":"e_1_2_3_33_1","doi-asserted-by":"publisher","DOI":"10.1021\/j100445a006"},{"key":"e_1_2_3_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/0045-6535(84)90199-1"},{"key":"e_1_2_3_35_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.3c01042"},{"key":"e_1_2_3_36_1","doi-asserted-by":"publisher","DOI":"10.1039\/c3sc51985f"}],"container-title":["Angewandte Chemie International Edition"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/anie.202405605","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T23:57:36Z","timestamp":1757462256000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/anie.202405605"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,26]]},"references-count":36,"journal-issue":{"issue":"31","published-print":{"date-parts":[[2024,7,29]]}},"alternative-id":["10.1002\/anie.202405605"],"URL":"https:\/\/doi.org\/10.1002\/anie.202405605","archive":["Portico"],"relation":{},"ISSN":["1433-7851","1521-3773"],"issn-type":[{"value":"1433-7851","type":"print"},{"value":"1521-3773","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,26]]},"assertion":[{"value":"2024-03-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-06-26","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e202405605"}}