{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T06:58:31Z","timestamp":1777359511368,"version":"3.51.4"},"reference-count":74,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T00:00:00Z","timestamp":1775692800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T00:00:00Z","timestamp":1775692800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2026,4,14]]},"abstract":"<jats:p>\n                    Parkinson's disease (PD) is a prevalent age\u2010related neurodegenerative syndrome, partially thought to be caused by a decrease in \u03b1\u2010synuclein proteostasis. Anle138b\u2009=\u20095\u2010(1,3\u2010benzodioxol\u20105\u2010yl)\u20103\u2010(3\u2010bromophenyl)\u20101\n                    <jats:italic>H<\/jats:italic>\n                    \u2010pyrazole (\n                    <jats:bold>HL<\/jats:bold>\n                    ) is undergoing clinical trials as a promising mitigator of \u03b1\u2010synuclein aggregation. Because complexation to metals is known to modulate the activity of several drugs, we have prepared and characterized:\n                    <jats:bold>H<\/jats:bold>\n                    <jats:sub>\n                      <jats:bold>2<\/jats:bold>\n                    <\/jats:sub>\n                    <jats:bold>L(ClO<\/jats:bold>\n                    <jats:sub>\n                      <jats:bold>4<\/jats:bold>\n                    <\/jats:sub>\n                    <jats:bold>)<\/jats:bold>\n                    ,\n                    <jats:bold>[Cu<\/jats:bold>\n                    <jats:sup>\n                      <jats:bold>I<\/jats:bold>\n                    <\/jats:sup>\n                    <jats:bold>(<\/jats:bold>\n                    <jats:bold>\u00b5<\/jats:bold>\n                    <jats:bold>\u2010L)]<\/jats:bold>\n                    <jats:sub>\n                      <jats:bold>3<\/jats:bold>\n                    <\/jats:sub>\n                    , and\n                    <jats:bold>[Ag<\/jats:bold>\n                    <jats:sup>\n                      <jats:bold>I<\/jats:bold>\n                    <\/jats:sup>\n                    <jats:bold>(<\/jats:bold>\n                    <jats:bold>\u00b5<\/jats:bold>\n                    <jats:bold>\u2010L)]<\/jats:bold>\n                    <jats:sub>\n                      <jats:bold>3<\/jats:bold>\n                    <\/jats:sub>\n                    . To better understand the bioviability of these compounds, we monitored their effects in a cell culture model of \u03b1\u2010synuclein protein aggregation using human \u03b1\u2010synuclein preformed fibrils (PFFs). Using two different anti\u2010\u03b1\u2010synuclein antibodies, our data suggest that\n                    <jats:bold>[Ag<\/jats:bold>\n                    <jats:sup>\n                      <jats:bold>I<\/jats:bold>\n                    <\/jats:sup>\n                    <jats:bold>(<\/jats:bold>\n                    <jats:bold>\u00b5<\/jats:bold>\n                    <jats:bold>\u2010L)]<\/jats:bold>\n                    <jats:sub>\n                      <jats:bold>3<\/jats:bold>\n                    <\/jats:sub>\n                    decreases a C\u2010terminal truncated protein that is approximately 12.4 kDa, as well as increases the size and alters the shape of PFF\u2010induced aggregates. This indicates that\n                    <jats:bold>[Ag<\/jats:bold>\n                    <jats:sup>\n                      <jats:bold>I<\/jats:bold>\n                    <\/jats:sup>\n                    <jats:bold>(<\/jats:bold>\n                    <jats:bold>\u00b5<\/jats:bold>\n                    <jats:bold>\u2010L)]<\/jats:bold>\n                    <jats:sub>\n                      <jats:bold>3<\/jats:bold>\n                    <\/jats:sub>\n                    impacts aggregation in a manner different from\n                    <jats:bold>HL<\/jats:bold>\n                    and may serve as a novel tool for studying C\u2010terminal truncation\u2010related aggregation chemistry.\n                  <\/jats:p>","DOI":"10.1002\/cmdc.202500890","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T03:32:35Z","timestamp":1775791955000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Coordination of Anle138b to Silver Results in Selective Reduction of a C\u2010Terminal Truncated \u03b1\u2010Synuclein Protein and Increased Aggregate Size"],"prefix":"10.1002","volume":"21","author":[{"given":"Kelly L.","family":"Rue","sequence":"first","affiliation":[{"name":"Department of Chemistry &amp; Biochemistry and the Biomolecular Sciences Institute Florida International University  Miami Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susana","family":"Herrera","sequence":"additional","affiliation":[{"name":"Department of Chemistry &amp; Biochemistry and the Biomolecular Sciences Institute Florida International University  Miami Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhi\u2010Chun","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Chemistry &amp; Biochemistry and the Biomolecular Sciences Institute Florida International University  Miami Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Indranil","family":"Chakraborty","sequence":"additional","affiliation":[{"name":"Department of Chemistry &amp; Biochemistry and the Biomolecular Sciences Institute Florida International University  Miami Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeremy","family":"Tachiki","sequence":"additional","affiliation":[{"name":"Buck Institute for Research on Aging  Novato California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Josue","family":"Ballesteros","sequence":"additional","affiliation":[{"name":"Buck Institute for Research on Aging  Novato California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julie K.","family":"Andersen","sequence":"additional","affiliation":[{"name":"Buck Institute for Research on Aging  Novato California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gordon J.","family":"Lithgow","sequence":"additional","affiliation":[{"name":"Buck Institute for Research on Aging  Novato California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wisam A.","family":"Al Isawi","sequence":"additional","affiliation":[{"name":"Department of Chemistry Western Michigan University  Kalamazoo Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3120-3084","authenticated-orcid":false,"given":"Gellert","family":"Mezei","sequence":"additional","affiliation":[{"name":"Department of Chemistry Western Michigan University  Kalamazoo Michigan USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2321-2324","authenticated-orcid":false,"given":"Minna","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Buck Institute for Research on Aging  Novato California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9522-0369","authenticated-orcid":false,"given":"Raphael G.","family":"Raptis","sequence":"additional","affiliation":[{"name":"Department of Chemistry &amp; Biochemistry and the Biomolecular Sciences Institute Florida International University  Miami Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,4,9]]},"reference":[{"key":"e_1_2_11_2_1","volume-title":"StatPearls","author":"Zafar S.","year":"2023"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.3233\/JPD-181474"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.13916"},{"issue":"1","key":"e_1_2_11_5_1","first-page":"742128","article-title":"High Prevalence of Gastroesophageal Reflux Disease in Parkinson's Disease: A Questionnaire\u2010Based Study","volume":"2013","author":"Maeda T.","year":"2013","journal-title":"Journal of Parkinson's Disease"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000200113"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-024-01853-0"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00702-002-0808-2"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24448"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/nan.12298"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-019-02040-w"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awaa238"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi5002536"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.92295"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-21027-4"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-023-04884-1"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1101738"},{"key":"e_1_2_11_18_1","first-page":"772","article-title":"Dopamine\u2010modified \u03b1\u2010synuclein blocks chaperone\u2010mediated autophagy","volume":"118","author":"Martinez\u2010Vicente M.","year":"2008","journal-title":"Journal of Clinical Investigation"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2018.00621"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-018-0257-5"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.5607\/en23007"},{"key":"e_1_2_11_22_1","unstructured":"J.Horsager \u201cParkinsonism (2024). (details pending journal and volume information)."},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.14808"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-21937-3"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-022-01140-3"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.3233\/JPD-140491"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1159\/000479653"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.3233\/JPD-191702"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(03)00367-3"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2017.09.005"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep39171"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-019-0423-2"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(23)00109-6"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000011337"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1609291113"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.7b07403"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2018.10.003"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA118.005603"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-022-03059-8"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-022-03768-0"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.REV120.011743"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5314-13.2014"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-017-0511-y"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2022.104021"},{"issue":"1","key":"e_1_2_11_45_1","article-title":"Anle138b\u2010P1\u201002: A Randomised, Double\u2010Blinded, Placebo\u2010Controlled Phase 1b Study to Investigate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of the Oligomer Modulator Anle138b in Parkinson\u00b4s Disease","volume":"38","author":"Levin J.","year":"2023","journal-title":"Movement Disorders"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2015.05.021"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-32797-w"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymeth.2023.04.002"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1039\/D0DT01365J"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/chem.201805985"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41570-018-0018-6"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1039\/C4MT00069B"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsmedchemlett.2c00441"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsmedchemlett.2c00116"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.2c01605"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom10020195"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41531-023-00604-y"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201405936"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1039\/D2QI01648F"},{"key":"e_1_2_11_60_1","volume-title":"the Assay Guidance Manual","author":"Riss T. L.","year":"2013"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-019-0696-4"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.66.3.34"},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41551\u2010025\u201001496\u20104"},{"key":"e_1_2_11_64_1","doi-asserted-by":"publisher","DOI":"10.1110\/ps.035592.108"},{"key":"e_1_2_11_65_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-013-1114-9"},{"key":"e_1_2_11_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2014.02.009"},{"key":"e_1_2_11_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2008.10.010"},{"key":"e_1_2_11_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2024.106077"},{"key":"e_1_2_11_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chempr.2023.12.004"},{"key":"e_1_2_11_70_1","doi-asserted-by":"publisher","DOI":"10.1039\/D3SC04182D"},{"key":"e_1_2_11_71_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.inorgchem.9b00991"},{"key":"e_1_2_11_72_1","volume-title":"APEX3","year":"2020"},{"key":"e_1_2_11_73_1","volume-title":"SAINT\u2010NT Software Reference Manual, Version 4.0","year":"1996"},{"key":"e_1_2_11_74_1","doi-asserted-by":"publisher","DOI":"10.1107\/S2053273314026370"},{"key":"e_1_2_11_75_1","doi-asserted-by":"publisher","DOI":"10.1107\/S2053229614024218"}],"container-title":["ChemMedChem"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cmdc.202500890","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cmdc.202500890","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cmdc.202500890","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T06:18:46Z","timestamp":1777357126000},"score":1,"resource":{"primary":{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/10.1002\/cmdc.202500890"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,9]]},"references-count":74,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,4,14]]}},"alternative-id":["10.1002\/cmdc.202500890"],"URL":"https:\/\/doi.org\/10.1002\/cmdc.202500890","archive":["Portico"],"relation":{},"ISSN":["1860-7179","1860-7187"],"issn-type":[{"value":"1860-7179","type":"print"},{"value":"1860-7187","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,9]]},"assertion":[{"value":"2025-10-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e202500890"}}