{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T22:29:42Z","timestamp":1791930582038,"version":"4.3.4"},"reference-count":24,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2013,7,17]],"date-time":"2013-07-17T00:00:00Z","timestamp":1374019200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2013,10]]},"abstract":"<jats:p>Human islet amyloid polypeptide (<jats:styled-content style=\"fixed-case\">hIAPP<\/jats:styled-content>) is highly amyloidogenic, whereas its homologs in rodents are non\u2010amyloidogenic. This observed non\u2010amyloidogenecity of rodent IAPP has been attributed to substitutions by proline in a region of <jats:styled-content style=\"fixed-case\">IAPP<\/jats:styled-content> that forms the core of the fibril. By employing molecular dynamics simulation, we have analyzed effects of position\u2010specific proline substitution on amyloidogenesis of the core region of the <jats:styled-content style=\"fixed-case\">hIAPP<\/jats:styled-content> fibril (22\u201328). We depict that substitution to proline at the 25th position is primarily responsible for the loss of amyloidogenecity of the peptide. In addition, 25th and 26th double mutation to proline and valine has been observed to show significant fibril destabilizing ability. On the contrary, substitution at 28th position to proline has the least ability to destabilize the amyloid fibril. Results obtained from this study are particularly important to design variants of the existing antihyperglycemic drug with minimalistic mutation approach for use in patients with diabetes.<\/jats:p>","DOI":"10.1111\/cbdd.12172","type":"journal-article","created":{"date-parts":[[2013,6,11]],"date-time":"2013-06-11T15:22:46Z","timestamp":1370964166000},"page":"446-452","source":"Crossref","is-referenced-by-count":15,"title":["Pinpointing Proline Substitution to be Responsible for the Loss of Amyloidogenesis in <scp>IAPP<\/scp>"],"prefix":"10.1111","volume":"82","author":[{"given":"Sandipan","family":"Chakraborty","sequence":"first","affiliation":[{"name":"Saroj Mohan Institute of Technology Guptipara Hooghly 712512 India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barnali","family":"Mukherjee","sequence":"additional","affiliation":[{"name":"DOEACC Centre, Jadavpur University Kolkata 700032 India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soumalee","family":"Basu","sequence":"additional","affiliation":[{"name":"School of Biotechnology &amp; Biological Sciences West Bengal University of Technology BF\u2010142, Salt Lake, Sector\u20101 Kolkata 700064 India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,7,17]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"crossref","first-page":"1595","DOI":"10.2337\/diab.37.12.1595","article-title":"Banting lecture: role of insulin resistance in human disease","volume":"37","author":"Reaven G.M.","year":"1998","journal-title":"Diabetes"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.84.23.8628"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(87)90825-7"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00500385"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4439(01)00078-3"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.66.1.385"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1072994"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra023144"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-003-1304-4"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1000357"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(89)81467-X"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi301525e"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpc.2012.05.003"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpc.2010.12.007"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1999.3422"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1529\/biophysj.104.047076"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200804198"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.20291"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s008940100045"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-987X(199709)18:12<1463::AID-JCC4>3.0.CO;2-H"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1021\/jp202640b"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi900998v"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1021\/jp9110794"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/bip.360221211"}],"container-title":["Chemical Biology &amp; Drug Design"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcbdd.12172","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cbdd.12172","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T03:59:35Z","timestamp":1696305575000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cbdd.12172"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,7,17]]},"references-count":24,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2013,10]]}},"alternative-id":["10.1111\/cbdd.12172"],"URL":"https:\/\/doi.org\/10.1111\/cbdd.12172","archive":["Portico"],"relation":{},"ISSN":["1747-0277","1747-0285"],"issn-type":[{"value":"1747-0277","type":"print"},{"value":"1747-0285","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,7,17]]}}}