{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T06:10:19Z","timestamp":1791007819954,"version":"4.1.0"},"reference-count":82,"publisher":"Wiley","issue":"21","license":[{"start":{"date-parts":[[2021,9,12]],"date-time":"2021-09-12T00:00:00Z","timestamp":1631404800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010146","name":"Alzheimer Forschung Initiative","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010146","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","award":["787679"],"award-info":[{"award-number":["787679"]}],"id":[{"id":"10.13039\/501100000781","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":[[2021,11,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Alzheimer's disease and other Tauopathies are associated with neurofibrillary tangles composed of Tau protein, as well as toxic Tau oligomers. Therefore, inhibitors of pathological Tau aggregation are potentially useful candidates for future therapies targeting Tauopathies. Two hexapeptides within Tau, designated PHF6* (275\u2010VQIINK\u2010280) and PHF6 (306\u2010VQIVYK\u2010311), are known to promote Tau aggregation. Recently, the PHF6* segment has been described as the more potent driver of Tau aggregation. We therefore employed mirror\u2010image phage display with a large peptide library to identify PHF6* fibril binding peptides consisting of D\u2010enantiomeric amino acids. The suitability of D\u2010enantiomeric peptides for\n                    <jats:italic>in\u2005vivo<\/jats:italic>\n                    applications, which are protease stable and less immunogenic than L\u2010peptides, has already been demonstrated. The identified D\u2010enantiomeric peptide MMD3 and its retro\u2010inverso form, designated MMD3rev, inhibited\n                    <jats:italic>in\u2005vitro<\/jats:italic>\n                    fibrillization of the PHF6* peptide, the repeat domain of Tau as well as full\u2010length Tau. Dynamic light scattering, pelleting assays and atomic force microscopy demonstrated that MMD3 prevents the formation of tau \u03b2\u2010sheet\u2010rich fibrils by diverting Tau into large amorphous aggregates. NMR data suggest that the D\u2010enantiomeric peptides bound to Tau monomers with rather low affinity, but ELISA (enzyme\u2010linked immunosorbent assay) data demonstrated binding to PHF6* and full length Tau fibrils. In addition, molecular insight into the binding mode of MMD3 to PHF6* fibrils were gained by\n                    <jats:italic>in silico<\/jats:italic>\n                    modelling. The identified PHF6*\u2010targeting peptides were able to penetrate cells. The study establishes PHF6* fibril binding peptides consisting of D\u2010enantiomeric amino acids as potential molecules for therapeutic and diagnostic applications in AD research.\n                  <\/jats:p>","DOI":"10.1002\/cbic.202100287","type":"journal-article","created":{"date-parts":[[2021,8,10]],"date-time":"2021-08-10T12:28:53Z","timestamp":1628598533000},"page":"3049-3059","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Potent Tau Aggregation Inhibitor D\u2010Peptides Selected against Tau\u2010Repeat 2 Using Mirror Image Phage Display"],"prefix":"10.1002","volume":"22","author":[{"given":"Marwa","family":"Malhis","sequence":"first","affiliation":[{"name":"Institut f\u00fcr Bioanalytik Hochschule f\u00fcr angewandte Wissenschaften  Coburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Senthilvelrajan","family":"Kaniyappan","sequence":"additional","affiliation":[{"name":"Deutsches Zentrum f\u00fcr Neurodegenerative Erkrankungen (DZNE)  Bonn Germany"},{"name":"Department of Neurodegenerative Diseases and Geriatric Psychiatry University of Bonn  Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Aillaud","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Bioanalytik Hochschule f\u00fcr angewandte Wissenschaften  Coburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ram Reddy","family":"Chandupatla","sequence":"additional","affiliation":[{"name":"Deutsches Zentrum f\u00fcr Neurodegenerative Erkrankungen (DZNE)  Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa Marie","family":"Ramirez","sequence":"additional","affiliation":[{"name":"Deutsches Zentrum f\u00fcr Neurodegenerative Erkrankungen (DZNE)  G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Zweckstetter","sequence":"additional","affiliation":[{"name":"Deutsches Zentrum f\u00fcr Neurodegenerative Erkrankungen (DZNE)  G\u00f6ttingen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anselm H. C.","family":"Horn","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Biochemie Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg  Erlangen Germany"},{"name":"Institut f\u00fcr Medizinische Genetik Universit\u00e4t Z\u00fcrich Schlieren  Z\u00fcrich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eckhard","family":"Mandelkow","sequence":"additional","affiliation":[{"name":"Deutsches Zentrum f\u00fcr Neurodegenerative Erkrankungen (DZNE)  Bonn Germany"},{"name":"Department of Neurodegenerative Diseases and Geriatric Psychiatry University of Bonn  Bonn Germany"},{"name":"CAESAR Research Center  Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heinrich","family":"Sticht","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Biochemie Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg  Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne Aileen","family":"Funke","sequence":"additional","affiliation":[{"name":"Institut f\u00fcr Bioanalytik Hochschule f\u00fcr angewandte Wissenschaften  Coburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,9,12]]},"reference":[{"key":"e_1_2_5_1_1","doi-asserted-by":"publisher","DOI":"10.1002\/ca.980080612"},{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.34.7.939"},{"key":"e_1_2_5_3_1","unstructured":"\u00a0"},{"key":"e_1_2_5_4_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.101.4.1371"},{"key":"e_1_2_5_5_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.16-11-03601.1996"},{"key":"e_1_2_5_6_1","first-page":"89","volume":"17","author":"Brion J. P.","year":"1985","journal-title":"J. Submicrosc. Cytol."},{"key":"e_1_2_5_7_1","unstructured":"\u00a0"},{"key":"e_1_2_5_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2015.04.043"},{"key":"e_1_2_5_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4328"},{"key":"e_1_2_5_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2017.04.002"},{"key":"e_1_2_5_11_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-020-00389-1"},{"key":"e_1_2_5_12_1","unstructured":"\u00a0"},{"key":"e_1_2_5_13_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.42.3.631"},{"key":"e_1_2_5_14_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1995.64020749.x"},{"key":"e_1_2_5_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410410106"},{"key":"e_1_2_5_16_1","unstructured":"\u00a0"},{"key":"e_1_2_5_17_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-019-0522-z"},{"key":"e_1_2_5_18_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-015-1483-3"},{"key":"e_1_2_5_19_1","unstructured":"\u00a0"},{"key":"e_1_2_5_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0908-894"},{"key":"e_1_2_5_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.02.040"},{"key":"e_1_2_5_22_2","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-019-0664-z"},{"key":"e_1_2_5_23_1","unstructured":"\u00a0"},{"key":"e_1_2_5_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.174.22.7235-7244.1992"},{"key":"e_1_2_5_25_2","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/S0022-3565(24)36388-8","volume":"280","author":"Pappenheimer J. R.","year":"1997","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"e_1_2_5_26_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M212694200"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1021\/cn100057j"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules24122237"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ssmph.2016.06.002"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules22101693"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.200800273"},{"key":"e_1_2_5_32_1","unstructured":"\u00a0"},{"key":"e_1_2_5_33_2","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.200800289"},{"key":"e_1_2_5_34_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-015-1791-2"},{"key":"e_1_2_5_35_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2017-018337"},{"key":"e_1_2_5_36_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-41993-6"},{"key":"e_1_2_5_37_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.97.10.5129"},{"key":"e_1_2_5_38_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M105196200"},{"key":"e_1_2_5_39_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.9.4.1381"},{"key":"e_1_2_5_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchem.2889"},{"key":"e_1_2_5_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10154"},{"key":"e_1_2_5_42_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0167432"},{"key":"e_1_2_5_43_1","volume":"2010","author":"Huang J.","year":"2010","journal-title":"J. Biomed. Biotechnol."},{"key":"e_1_2_5_44_1","unstructured":"\u00a0"},{"key":"e_1_2_5_45_2","doi-asserted-by":"crossref","first-page":"157","DOI":"10.14283\/jpad.2019.14","volume":"6","author":"Cummings J.","year":"2019","journal-title":"J. Prev. Alzheimer's Dis."},{"key":"e_1_2_5_46_2","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1685"},{"key":"e_1_2_5_47_1","unstructured":"\u00a0"},{"key":"e_1_2_5_48_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.n1682"},{"key":"e_1_2_5_49_2","doi-asserted-by":"publisher","DOI":"10.1002\/alz.12213"},{"key":"e_1_2_5_50_2","first-page":"496","volume":"20","author":"Mullard A.","year":"2021","journal-title":"Nat. Rev. Drug Discovery"},{"key":"e_1_2_5_51_1","unstructured":"\u00a0"},{"key":"e_1_2_5_52_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2194"},{"key":"e_1_2_5_53_2","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2013.00072"},{"key":"e_1_2_5_54_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00308809"},{"key":"e_1_2_5_55_1","unstructured":"\u00a0"},{"key":"e_1_2_5_56_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24546"},{"key":"e_1_2_5_57_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3182918ca6"},{"key":"e_1_2_5_58_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aww023"},{"key":"e_1_2_5_59_1","unstructured":"\u00a0"},{"key":"e_1_2_5_60_2","doi-asserted-by":"publisher","DOI":"10.1002\/chem.201504950"},{"key":"e_1_2_5_61_2","doi-asserted-by":"publisher","DOI":"10.1039\/C8CC01233D"},{"key":"e_1_2_5_62_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chempr.2016.08.002"},{"key":"e_1_2_5_63_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja110545h"},{"key":"e_1_2_5_64_1","unstructured":"\u00a0"},{"key":"e_1_2_5_65_2","doi-asserted-by":"publisher","DOI":"10.1097\/WAD.0b013e31815bf5e5"},{"key":"e_1_2_5_66_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2017.05.003"},{"key":"e_1_2_5_67_1","unstructured":"\u00a0"},{"key":"e_1_2_5_68_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature23002"},{"key":"e_1_2_5_69_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-018-1914-z"},{"key":"e_1_2_5_70_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-021-02294-3"},{"key":"e_1_2_5_71_1","doi-asserted-by":"publisher","DOI":"10.1021\/acschemneuro.9b00458"},{"key":"e_1_2_5_72_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-16565-1"},{"key":"e_1_2_5_73_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA120.014630"},{"key":"e_1_2_5_74_1","unstructured":"\u00a0"},{"key":"e_1_2_5_75_2","doi-asserted-by":"publisher","DOI":"10.1039\/C9SC01331H"},{"key":"e_1_2_5_76_2","doi-asserted-by":"publisher","DOI":"10.1021\/cb500505m"},{"key":"e_1_2_5_77_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2016.03.035"},{"key":"e_1_2_5_78_1","unstructured":"\u00a0"},{"key":"e_1_2_5_79_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2004.10.009"},{"key":"e_1_2_5_80_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)34080-2"},{"key":"e_1_2_5_81_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2007.08.002"},{"key":"e_1_2_5_82_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201601147"}],"container-title":["ChemBioChem"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cbic.202100287","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cbic.202100287","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cbic.202100287","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T08:42:04Z","timestamp":1760258524000},"score":1,"resource":{"primary":{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/10.1002\/cbic.202100287"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,12]]},"references-count":82,"journal-issue":{"issue":"21","published-print":{"date-parts":[[2021,11,3]]}},"alternative-id":["10.1002\/cbic.202100287"],"URL":"https:\/\/doi.org\/10.1002\/cbic.202100287","archive":["Portico"],"relation":{},"ISSN":["1439-4227","1439-7633"],"issn-type":[{"value":"1439-4227","type":"print"},{"value":"1439-7633","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,12]]},"assertion":[{"value":"2021-06-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-09-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}