{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T00:51:48Z","timestamp":1760316708033,"version":"build-2065373602"},"reference-count":81,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T00:00:00Z","timestamp":1750118400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003407","name":"Ministero dell\u2019Istruzione, dell\u2019Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","award":["DN. 1553 11.10.2022"],"award-info":[{"award-number":["DN. 1553 11.10.2022"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020581","name":"Fondazione AIRC per la ricerca sul cancro ETS","doi-asserted-by":"publisher","award":["IG 2022","Rif. 27378"],"award-info":[{"award-number":["IG 2022","Rif. 27378"]}],"id":[{"id":"10.13039\/100020581","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemBioChem"],"published-print":{"date-parts":[[2025,7,18]]},"abstract":"<jats:p>Nucleophosmin 1(NPM1) is an abundant human protein endowed with many functions where whose dysregulation leads to various cancers and mutations are relevant in acute myeloid leukemia (AML). In the wild\u2010type form, pentameric NPM1 resides mainly in the nucleolus even if it shuttles toward the cytosol exerting its chaperon function; conversely in AML\u2010mutated versions, it has mainly a cytoplasmic localization, hence the name NPMc+. All types of AML mutations determine an important amyloid aggregation propensity of the C\u2010terminal domains (CTD) of NPMc+\u2009and to exploit this amyloidogenicity for therapeutical purposes; herein, this study presents the design and structural and functional investigations of a series of peptides analogs of the sequence of the second helix of the three\u2010helix bundle of the wt CTD as potential enhancers of amyloid aggregation. Peptides are designed by introducing conservative mutations in the native 264\u2212277 fragment, and their structural features and amyloid propensities are assessed through ThT fluorescence, circular dichroism spectroscopies and scanning electron microscopy. Several \u201caccelerator sequences\u201d are employed in amyloid seeding assays (ASAs): The sequence NPM1<jats:sub>264\u2010277<\/jats:sub> K<jats:sub>267<\/jats:sub>R, with the single mutation Lys<jats:sup>267<\/jats:sup>\/Arg, exhibits the greater ability to act as a promoter of the amyloid aggregation of NPM1<jats:sub>264\u2010277<\/jats:sub>, limiting its toxicity and rescuing cell viability in OCI\u2010AML3 cells.<\/jats:p>","DOI":"10.1002\/cbic.202500306","type":"journal-article","created":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T02:29:01Z","timestamp":1747880941000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Peptidomimetics Targeting the Amyloidogenicity of Nucleophosmin 1 Mutations in Acute Myeloid Leukemia"],"prefix":"10.1002","volume":"26","author":[{"given":"Daniele","family":"Florio","sequence":"first","affiliation":[{"name":"Department of Pharmacy University of Naples \u201cFederico II\u201d  80131 Naples Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"La Manna","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Naples \u201cFederico II\u201d  80131 Naples Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giada Raffaella","family":"Fiore","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Naples \u201cFederico II\u201d  80131 Naples Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valentina","family":"Roviello","sequence":"additional","affiliation":[{"name":"Department of Agriculture University of Naples \u201cFederico II\u201d  80055 Naples Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuliano","family":"Castellano","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Science University of Naples \u201cFederico II\u201d  80131 Naples Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sossio Fabio","family":"Graziano","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Naples \u201cFederico II\u201d  80131 Naples Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna Maria","family":"Malfitano","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Science University of Naples \u201cFederico II\u201d  80131 Naples Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6618-2949","authenticated-orcid":false,"given":"Daniela","family":"Marasco","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Naples \u201cFederico II\u201d  80131 Naples Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,6,17]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2021.08.013"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.22615"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biochem-061516-045115"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/35065514"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0915166107"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2018.05.046"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1067484"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0040006"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1173155"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2016.09.054"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.04.017"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0910163107"},{"key":"e_1_2_8_14_1","unstructured":"J. G.Beton J.Monistrol A.Wentink E. C.Johnston A. J.Roberts B.Bukau B. W.Hoogenboom H. R.Saibil bioRxiv2021."},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-019-0423-2"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature23002"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2317-6"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4809-05.2006"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1100976108"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0800712105"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.182426599"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20040829"},{"key":"e_1_2_8_23_1","volume":"12","author":"Florio D.","year":"2019","journal-title":"Pharm. Basel"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.biochem.0c00328"},{"key":"e_1_2_8_25_1","volume":"13","author":"Florio D.","year":"2020","journal-title":"Pharm. Basel"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2020.109300"},{"key":"e_1_2_8_27_1","volume":"22","author":"Manna S.","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.719"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.592527"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.sbi.2014.12.004"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/npjparkd.2015.24"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200901694"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2022.106001"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrestox.1c00089"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-28660-7"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0039369"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/jps.21566"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2010.02.025"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2021108591"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2018.04.020"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btm325"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-10-S1-S45"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.1432"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ab.2020.113691"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41557-023-01289-9"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.03.076"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2019.08.013"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1155\/2011\/195209"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1093\/jb\/mvm222"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12867-016-0073-9"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/prot.21504"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1321007111"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.25.17.7534-7545.2005"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi101835j"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.14407"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-03255-3"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-015-0125-7"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.13571"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M003278200"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2008.02.059"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.14-269522"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.10991"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2018.01.005"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbapap.2019.01.010"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2018.10.210"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.14815"},{"key":"e_1_2_8_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2020.08.248"},{"key":"e_1_2_8_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.colsurfb.2020.111439"},{"key":"e_1_2_8_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2021.104997"},{"key":"e_1_2_8_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2021.08.023"},{"key":"e_1_2_8_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2022.130173"},{"key":"e_1_2_8_72_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.8599"},{"key":"e_1_2_8_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbapap.2017.03.004"},{"key":"e_1_2_8_74_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2024.107404"},{"key":"e_1_2_8_75_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.inorgchem.3c01522"},{"key":"e_1_2_8_76_1","doi-asserted-by":"publisher","DOI":"10.1039\/D3DT02187D"},{"key":"e_1_2_8_77_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2021.105047"},{"key":"e_1_2_8_78_1","doi-asserted-by":"publisher","DOI":"10.1039\/D2SM01385A"},{"key":"e_1_2_8_79_1","doi-asserted-by":"publisher","DOI":"10.1039\/D3DT01110K"},{"key":"e_1_2_8_80_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1500851112"},{"key":"e_1_2_8_81_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0025020"},{"key":"e_1_2_8_82_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-00842-8"}],"container-title":["ChemBioChem"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cbic.202500306","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T18:25:08Z","timestamp":1760293508000},"score":1,"resource":{"primary":{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/10.1002\/cbic.202500306"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,17]]},"references-count":81,"journal-issue":{"issue":"14","published-print":{"date-parts":[[2025,7,18]]}},"alternative-id":["10.1002\/cbic.202500306"],"URL":"https:\/\/doi.org\/10.1002\/cbic.202500306","archive":["Portico"],"relation":{},"ISSN":["1439-4227","1439-7633"],"issn-type":[{"type":"print","value":"1439-4227"},{"type":"electronic","value":"1439-7633"}],"subject":[],"published":{"date-parts":[[2025,6,17]]},"assertion":[{"value":"2025-04-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e202500306"}}