{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T12:06:11Z","timestamp":1787313971948,"version":"build-2736575974"},"reference-count":50,"publisher":"Wiley","issue":"23","license":[{"start":{"date-parts":[[2017,11,2]],"date-time":"2017-11-02T00:00:00Z","timestamp":1509580800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["200021-159713"],"award-info":[{"award-number":["200021-159713"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003006","name":"Eidgen\u00f6ssische Technische Hochschule Z\u00fcrich","doi-asserted-by":"publisher","award":["ETH-08 15-1"],"award-info":[{"award-number":["ETH-08 15-1"]}],"id":[{"id":"10.13039\/501100003006","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["CRC 765, Project C10"],"award-info":[{"award-number":["CRC 765, Project C10"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemPhysChem"],"published-print":{"date-parts":[[2017,12,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Cyclic peptides have regained interest as potential inhibitors of challenging targets but have often a low bioavailability. The natural product cyclosporine\u2005A (CsA) is the textbook exception. Despite its size and polar backbone, it is able to passively cross membranes. This ability is hypothesized to be due to a conformational change from the low\u2010energy conformation in water to a \u201ccongruent\u201d conformation that is populated both in water and inside the membrane. Here, we use a combination of NMR measurements and kinetic models based on molecular dynamics simulations to rationalize the difference in the membrane permeability of cyclosporine\u2005E (CsE) and CsA. The structure of CsE differs only in a backbone methylation, but its membrane permeability is one order of magnitude lower. The most striking difference is found in the interconversion rates between the conformational states favored in water and in chloroform, which are up to one order of magnitude slower for CsE compared to CsA.<\/jats:p>","DOI":"10.1002\/cphc.201700995","type":"journal-article","created":{"date-parts":[[2017,9,18]],"date-time":"2017-09-18T10:19:16Z","timestamp":1505729956000},"page":"3309-3314","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":62,"title":["Interconversion Rates between Conformational States as Rationale for the Membrane Permeability of Cyclosporines"],"prefix":"10.1002","volume":"18","author":[{"given":"Jagna","family":"Witek","sequence":"first","affiliation":[{"name":"Laboratory of Physical Chemistry ETH Z\u00fcrich  Vladimir-Prelog-Weg 2 8093 Z\u00fcrich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Max","family":"M\u00fchlbauer","sequence":"additional","affiliation":[{"name":"Laboratory of Physical Chemistry ETH Z\u00fcrich  Vladimir-Prelog-Weg 2 8093 Z\u00fcrich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bettina G.","family":"Keller","sequence":"additional","affiliation":[{"name":"Department of Biology, Chemistry, Pharmacy Freie Universit\u00e4t Berlin  Takustrasse 3 14195 Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Blatter","sequence":"additional","affiliation":[{"name":"Novartis Institutes for BioMedical Research Novartis Pharma AG  Novartis Campus 4056 Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Axel","family":"Meissner","sequence":"additional","affiliation":[{"name":"Novartis Institutes for BioMedical Research Novartis Pharma AG  Novartis Campus 4056 Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trixie","family":"Wagner","sequence":"additional","affiliation":[{"name":"Novartis Institutes for BioMedical Research Novartis Pharma AG  Novartis Campus 4056 Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1893-4031","authenticated-orcid":false,"given":"Sereina","family":"Riniker","sequence":"additional","affiliation":[{"name":"Laboratory of Physical Chemistry ETH Z\u00fcrich  Vladimir-Prelog-Weg 2 8093 Z\u00fcrich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,11,2]]},"reference":[{"key":"e_1_2_2_1_1","unstructured":"\u00a0"},{"key":"e_1_2_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2590"},{"key":"e_1_2_2_3_2","doi-asserted-by":"publisher","DOI":"10.1517\/17460441.2011.632002"},{"key":"e_1_2_2_4_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm1012374"},{"key":"e_1_2_2_5_2","doi-asserted-by":"publisher","DOI":"10.4155\/fmc.12.93"},{"key":"e_1_2_2_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.1584"},{"key":"e_1_2_2_7_2","doi-asserted-by":"publisher","DOI":"10.1039\/C4SC03089C"},{"key":"e_1_2_2_8_2","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.5b01286"},{"key":"e_1_2_2_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0169-409X(00)00129-0"},{"key":"e_1_2_2_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1056-8719(00)00107-6"},{"key":"e_1_2_2_11_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pa.34.040194.001541"},{"key":"e_1_2_2_12_1","doi-asserted-by":"publisher","DOI":"10.1039\/c2md20203d"},{"key":"e_1_2_2_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/bip.22878"},{"key":"e_1_2_2_14_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr900238d"},{"key":"e_1_2_2_15_1","unstructured":"\u00a0"},{"key":"e_1_2_2_16_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01870176"},{"key":"e_1_2_2_17_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01870127"},{"key":"e_1_2_2_18_2","doi-asserted-by":"publisher","DOI":"10.1021\/j100066a040"},{"key":"e_1_2_2_19_2","doi-asserted-by":"publisher","DOI":"10.1021\/jp952956f"},{"key":"e_1_2_2_20_1","doi-asserted-by":"publisher","DOI":"10.1021\/jp035260s"},{"key":"e_1_2_2_21_1","doi-asserted-by":"publisher","DOI":"10.1529\/biophysj.103.030601"},{"key":"e_1_2_2_22_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jcim.6b00022"},{"key":"e_1_2_2_23_1","doi-asserted-by":"publisher","DOI":"10.1021\/ct500209j"},{"key":"e_1_2_2_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep35913"},{"key":"e_1_2_2_25_1","volume-title":"Cyclosporin A","year":"1982"},{"key":"e_1_2_2_26_1","unstructured":"\u00a0"},{"key":"e_1_2_2_27_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja0563455"},{"key":"e_1_2_2_28_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja063076p"},{"key":"e_1_2_2_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/prot.21855"},{"key":"e_1_2_2_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/hlca.19850680319"},{"key":"e_1_2_2_31_1","doi-asserted-by":"publisher","DOI":"10.1021\/ci200583t"},{"key":"e_1_2_2_32_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jcim.6b00005"},{"key":"e_1_2_2_33_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jcim.6b00251"},{"key":"e_1_2_2_34_1","unstructured":"\u00a0"},{"key":"e_1_2_2_35_2","doi-asserted-by":"publisher","DOI":"10.1006\/jcph.1999.6231"},{"key":"e_1_2_2_36_2","doi-asserted-by":"publisher","DOI":"10.1021\/jp037421y"},{"key":"e_1_2_2_37_2","doi-asserted-by":"publisher","DOI":"10.1063\/1.3565032"},{"key":"e_1_2_2_38_2","doi-asserted-by":"publisher","DOI":"10.1063\/1.4965440"},{"key":"e_1_2_2_39_1","doi-asserted-by":"publisher","DOI":"10.1063\/1.4909549"},{"key":"e_1_2_2_39_2","doi-asserted-by":"publisher","DOI":"10.1137\/090764049"},{"key":"e_1_2_2_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11030-014-9514-x"},{"key":"e_1_2_2_41_1","doi-asserted-by":"publisher","DOI":"10.4155\/fmc.15.78"},{"key":"e_1_2_2_42_1","doi-asserted-by":"publisher","DOI":"10.1135\/cccc19980115"},{"key":"e_1_2_2_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cpc.2011.12.014"},{"key":"e_1_2_2_44_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00249-011-0700-9"},{"key":"e_1_2_2_45_1","unstructured":"\u00a0"},{"key":"e_1_2_2_46_2","doi-asserted-by":"publisher","DOI":"10.1021\/jp0356620"},{"key":"e_1_2_2_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-2614(97)01198-6"},{"key":"e_1_2_2_48_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jcim.7b00502"},{"key":"e_1_2_2_49_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm060230"}],"container-title":["ChemPhysChem"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcphc.201700995","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cphc.201700995","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T14:00:19Z","timestamp":1760364019000},"score":1,"resource":{"primary":{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/10.1002\/cphc.201700995"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,11,2]]},"references-count":50,"journal-issue":{"issue":"23","published-print":{"date-parts":[[2017,12,6]]}},"alternative-id":["10.1002\/cphc.201700995"],"URL":"https:\/\/doi.org\/10.1002\/cphc.201700995","archive":["Portico"],"relation":{},"ISSN":["1439-4235","1439-7641"],"issn-type":[{"value":"1439-4235","type":"print"},{"value":"1439-7641","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,11,2]]},"assertion":[{"value":"2017-09-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-11-02","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}