{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T06:16:29Z","timestamp":1789193789637,"version":"build-2803163510"},"reference-count":85,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2015,5,23]],"date-time":"2015-05-23T00:00:00Z","timestamp":1432339200000},"content-version":"vor","delay-in-days":22,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"European Union (European Regional Development Fund\u2013ERDF) and Greek national funds through the Operational Program \u201cCompetitiveness and Entrepreneurship\u201d of the National Strategic Reference Framework (NSRF)","award":["11SYN-1-1230"],"award-info":[{"award-number":["11SYN-1-1230"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biopolymers"],"published-print":{"date-parts":[[2015,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Amyloid deposits to the islets of Langerhans are responsible for the gradual loss of pancreatic \u03b2\u2010cells leading to type II diabetes mellitus. Human mature islet amyloid polypeptide (hIAPP), a 37\u2010residue pancreatic hormone, has been identified as the primary component of amyloid fibrils forming these deposits. Several individual segments along the entire sequence length of hIAPP have been nominated as regions with increased amyloidogenic potential, such as regions 8\u201320, 20\u201329, and 30\u201337. A smaller fragment of the 8\u201320 region, spanning residues 8\u201316 of hIAPP has been associated with the formation of early transient \u03b1\u2010helical dimers that promote fibrillogenesis and also as a core part of hIAPP amyloid fibrils. Utilizing our aggregation propensity prediction tools AmylPred and AmylPred2, we have identified the high aggregation propensity of the 8\u201316 segment of hIAPP. A peptide analog corresponding to this segment was chemically synthesized and its amyloidogenic properties were validated using electron microscopy, X\u2010ray fiber diffraction, ATR FT\u2010IR spectroscopy, and polarized microscopy. Additionally, two peptides introducing point mutations L12R and L12P, respectively, to the 8\u201316 segment, were chemically synthesized. Both mutations disrupt the \u03b1\u2010helical properties of the 8\u201316 region and lower its amyloidogenic potential, which was confirmed experimentally. Finally, cytotoxicity assays indicate that the 8\u201316 segment of hIAPP shows enhanced cytotoxicity, which is relieved by the L12R mutation but not by the L12P mutation. Our results indicate that the chameleon properties and the high aggregation propensity of the 8\u201316 region may significantly contribute to the formation of amyloid fibrils and the overall cytotoxic effect of hIAPP. \u00a9 2015 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 104: 196\u2013205, 2015.<\/jats:p>","DOI":"10.1002\/bip.22650","type":"journal-article","created":{"date-parts":[[2015,4,25]],"date-time":"2015-04-25T13:52:56Z","timestamp":1429969976000},"page":"196-205","source":"Crossref","is-referenced-by-count":22,"title":["Structural studies and cytotoxicity assays of \u201caggregation\u2010prone\u201d IAPP<sub>8\u201316<\/sub> and its non\u2010amyloidogenic variants suggest its important role in fibrillogenesis and cytotoxicity of human amylin"],"prefix":"10.1002","volume":"104","author":[{"given":"Nikolaos N.","family":"Louros","sequence":"first","affiliation":[{"name":"Department of Cell Biology and Biophysics Faculty of Biology, University of Athens Panepistimiopolis Athens 157 01 Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paraskevi L.","family":"Tsiolaki","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Biophysics Faculty of Biology, University of Athens Panepistimiopolis Athens 157 01 Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aikaterini A.","family":"Zompra","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Patras Patras 26504 Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleni V.","family":"Pappa","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Patras Patras 26504 Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vassiliki","family":"Magafa","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Patras Patras 26504 Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Pairas","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Patras Patras 26504 Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Cordopatis","sequence":"additional","affiliation":[{"name":"Department of Pharmacy University of Patras Patras 26504 Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Cheimonidou","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Biophysics Faculty of Biology, University of Athens Panepistimiopolis Athens 157 01 Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioannis P.","family":"Trougakos","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Biophysics Faculty of Biology, University of Athens Panepistimiopolis Athens 157 01 Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vassiliki A.","family":"Iconomidou","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Biophysics Faculty of Biology, University of Athens Panepistimiopolis Athens 157 01 Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stavros J.","family":"Hamodrakas","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Biophysics Faculty of Biology, University of Athens Panepistimiopolis Athens 157 01 Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,5,23]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)77825-9"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4827(89)90407-2"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(89)81260-8"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00042.2009"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/30666"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo.140.6.6930"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463-1326.2012.01670.x"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00213.2004"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.physbeh.2010.03.001"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-24716-3_10"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s001250050646"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00703.2009"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-011-0905-1"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2013.01.017"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/1472-6807-9-44"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2634884100"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1039\/c3cc39052g"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.3109\/13506129.2012.734345"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(87)90825-7"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01660981"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00274799"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2008-1070828"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/bies.950090109"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.13.5036"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1999.3286"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1999.3422"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M102883200"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2836(02)00887-2"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.2001.4593"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1047-8477(02)00630-5"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1021\/jp108870q"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0054175"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja1069882"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/pro.145"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1102971108"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4039(00)99290-6"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0073258"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2013.10.049"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/bip.22563"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/bip.21698"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00544254"},{"key":"e_1_2_7_43_1","unstructured":"Oxford Diffraction. Chrysalis Promotions; In: Diffraction Ed.; Oxford Diffraction Ltd.: Abingdon Oxfordshire England 2009."},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4020-6316-9_4"},{"key":"e_1_2_7_44_2","first-page":"41","volume":"245","author":"Read R.","journal-title":"Evolving Methods for Macromolecular Crystallography"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1021\/ac60214a047"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2014.05.038"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2010.11.050"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsb.2008.12.011"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1088\/0034-4885\/76\/4\/046601"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-4622(99)00060-5"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/bip.360370404"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-3233(08)60528-8"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1745-7270.2007.00320.x"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.3109\/10409239509085140"},{"key":"e_1_2_7_55_1","first-page":"1808","volume":"97","author":"Divry D.","year":"1927","journal-title":"Comptes Rendus de la Societe de Biologie"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsb.2003.10.004"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2013.01.031"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1998.9574"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.48.3.491"},{"key":"e_1_2_7_60_1","doi-asserted-by":"publisher","DOI":"10.1038\/368756a0"},{"key":"e_1_2_7_61_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1998.2299"},{"key":"e_1_2_7_62_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1999.2646"},{"key":"e_1_2_7_63_1","doi-asserted-by":"publisher","DOI":"10.1006\/jsbi.2000.4268"},{"key":"e_1_2_7_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinorgbio.2010.05.012"},{"key":"e_1_2_7_65_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi701427q"},{"key":"e_1_2_7_66_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0805957106"},{"key":"e_1_2_7_67_1","doi-asserted-by":"publisher","DOI":"10.1093\/protein\/gzp036"},{"key":"e_1_2_7_68_1","doi-asserted-by":"publisher","DOI":"10.1088\/1478-3975\/6\/1\/015005"},{"key":"e_1_2_7_69_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbic.200900237"},{"key":"e_1_2_7_70_1","doi-asserted-by":"publisher","DOI":"10.1021\/ar200189b"},{"key":"e_1_2_7_71_1","doi-asserted-by":"publisher","DOI":"10.1021\/jz5001775"},{"key":"e_1_2_7_72_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi3012548"},{"key":"e_1_2_7_73_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja900285z"},{"key":"e_1_2_7_74_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi3009888"},{"key":"e_1_2_7_75_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja1007867"},{"key":"e_1_2_7_76_1","doi-asserted-by":"publisher","DOI":"10.1039\/c3cc40383a"},{"key":"e_1_2_7_77_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2012.11.3811"},{"key":"e_1_2_7_78_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2010.09.070"},{"key":"e_1_2_7_79_1","doi-asserted-by":"publisher","DOI":"10.1039\/c3cp44696d"},{"key":"e_1_2_7_80_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2007.07.001"},{"key":"e_1_2_7_81_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja710484d"},{"key":"e_1_2_7_82_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi801427c"},{"key":"e_1_2_7_83_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi8014357"},{"key":"e_1_2_7_84_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2011.06.012"},{"key":"e_1_2_7_85_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja9010095"}],"container-title":["Peptide Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fbip.22650","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fbip.22650","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bip.22650","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/bip.22650","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bip.22650","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,19]],"date-time":"2023-08-19T16:49:18Z","timestamp":1692463758000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/bip.22650"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,5]]},"references-count":85,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2015,5]]}},"alternative-id":["10.1002\/bip.22650"],"URL":"https:\/\/doi.org\/10.1002\/bip.22650","archive":["Portico"],"relation":{},"ISSN":["0006-3525"],"issn-type":[{"value":"0006-3525","type":"print"}],"subject":[],"published":{"date-parts":[[2015,5]]}}}