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For this purpose, a number of regioselective, semiregioselective, and random strategies have been studied. In addition to selecting distinct protecting groups for the thiol function, their position in the sequence, the influence of the neighboring protecting groups, as well as the order in which the disulfides fold were studied. Here we describe an optimized solid\u2010phase synthesis of linaclotide that should allow the production of this peptide in multigram amounts. \u00a9 2010 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 96: 69\u201380, 2011.<\/jats:p>","DOI":"10.1002\/bip.21480","type":"journal-article","created":{"date-parts":[[2010,6,25]],"date-time":"2010-06-25T14:31:00Z","timestamp":1277476260000},"page":"69-80","source":"Crossref","is-referenced-by-count":64,"title":["Optimized Fmoc solid\u2010phase synthesis of the cysteine\u2010rich peptide linaclotide"],"prefix":"10.1002","volume":"96","author":[{"given":"Miriam","family":"G\u00f3ngora\u2010Ben\u00edtez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judit","family":"Tulla\u2010Puche","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Parad\u00eds\u2010Bas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oleg","family":"Werbitzky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthieu","family":"Giraud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Albericio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2010,8,21]]},"reference":[{"key":"e_1_2_6_2_2","unstructured":"(a)Currie M. 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J.","year":"2007","journal-title":"Curr Opin Drug Discov Devel"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja00017a044"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9861(59)90090-6"},{"key":"e_1_2_6_24_2","first-page":"1","volume":"194","author":"Wu J.","year":"2002","journal-title":"Methods Mol Biol"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/bip.20270"},{"key":"e_1_2_6_26_2","unstructured":"Kessler M. M.;Wakefield J. D.;Jing Sun L.;Fretzen A.;Busby R. W.Mass Spectrometry Characterization of Disulfide Bonds in Linaclotide (MD\u20101100) an Orally Administered Peptide Designed for the Treatment of IBS\u2010C. 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