{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T05:49:55Z","timestamp":1792043395181,"version":"4.4.0"},"reference-count":39,"publisher":"Wiley","issue":"18","license":[{"start":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T00:00:00Z","timestamp":1789862400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T00:00:00Z","timestamp":1789862400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100010218","name":"Department of Science and Technology, Philippines","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010218","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["GNT 2009564"],"award-info":[{"award-number":["GNT 2009564"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"publisher","award":["CE200100012"],"award-info":[{"award-number":["CE200100012"]}],"id":[{"id":"10.13039\/501100000923","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":[[2026,9,28]]},"abstract":"<jats:p>Cyclotides are peptides with a head\u2010to\u2010tail cyclic backbone and six cysteine residues that are linked in a knotted arrangement. Their unique structure confers exceptional stability and various biological activities, resulting in numerous studies on their synthesis and development for a range of applications. One challenge in cyclotide synthesis is the formation of the correct disulfide bonds that fold the peptide into the native conformation. Replacement of a native disulfide bond with the faster\u2010forming diselenide bond by substituting cysteine residues with selenocysteine is a strategy that can be implemented to overcome this issue. In this study, we synthesized selenocysteine analogs of the cyclotide kalata B2 and determined the effect of the substitution on folding, structure, and biological activity. The analogs folded faster than their native counterpart, implying that the diselenide bond assists in the formation of the correct structure. HPLC and nuclear magnetic resonance (NMR) analysis revealed a native\u2010like structure for all analogs. Cytotoxicity and membrane binding assays showed that biological activity was maintained upon selenocysteine substitution. Overall, this study demonstrates the conservative nature of diselenide replacement while improving the folding of kalata B2.<\/jats:p>","DOI":"10.1002\/cbic.70543","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T06:54:31Z","timestamp":1789973671000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effects of Selenocysteine Substitution on the Cyclotide Kalata B2"],"prefix":"10.1002","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-2348-3600","authenticated-orcid":false,"given":"Ramoncito Luis B.","family":"de Boda","sequence":"first","affiliation":[{"name":"Institute for Molecular Bioscience Australian Research Council Centre of Excellence for Innovations in Peptide and Protein Science The University of Queensland  Brisbane Queensland Australia"},{"name":"Institute of Chemistry College of Science University of the Philippines Diliman  Quezon City Philippines"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00f3nia Troeira","family":"Henriques","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience Australian Research Council Centre of Excellence for Innovations in Peptide and Protein Science The University of Queensland  Brisbane Queensland Australia"},{"name":"School of Biomedical Sciences, Centre for Microbiome Research, and Centre for Immunology and Infectious Control Faculty of Health Translational Research Institute Queensland University of Technology  Brisbane Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yen\u2010Hua","family":"Huang","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience Australian Research Council Centre of Excellence for Innovations in Peptide and Protein Science The University of Queensland  Brisbane Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine C.","family":"Hernandez","sequence":"additional","affiliation":[{"name":"Institute of Chemistry College of Science University of the Philippines Diliman  Quezon City Philippines"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Portia Mahal G.","family":"Sabido","sequence":"additional","affiliation":[{"name":"Institute of Chemistry College of Science University of the Philippines Diliman  Quezon City Philippines"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0007-6796","authenticated-orcid":false,"given":"David J.","family":"Craik","sequence":"additional","affiliation":[{"name":"Institute for Molecular Bioscience Australian Research Council Centre of Excellence for Innovations in Peptide and Protein Science The University of Queensland  Brisbane Queensland Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,20]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1999.3383"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M211147200"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi049711q"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2020.170430"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.accounts.7b00157"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0040\u20104039(97)01271\u20109"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/pro.v7:7"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi990605b"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbic.v9:1"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2010.3112"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi2007004"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00726\u2010012\u20101376\u2010x"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2008.2295"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/psc.1075"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003\u20109861(67)90136\u20101"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.v36:8"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1998.2189"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1110\/ps.8.8.1605"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/(ISSN)1097\u20100282"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M512419200"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200806085"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi902137c"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja910602h"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201101642"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1039\/c4sc02379j"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.v56.20"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/chem.v25.36"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42004\u2010023\u201001056\u20104"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42004\u2010021\u201000463\u20109"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/psc.v29.5"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1039\/D4CB00095A"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi047837h"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.372011"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbic.v15.13"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1593\/neo.101366"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nut.2012.11.012"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1021\/jo500699m"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/prot.v59:4"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00227471"}],"container-title":["ChemBioChem"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cbic.70543","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cbic.70543","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cbic.70543","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T05:43:48Z","timestamp":1792043028000},"score":1,"resource":{"primary":{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/10.1002\/cbic.70543"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,20]]},"references-count":39,"journal-issue":{"issue":"18","published-print":{"date-parts":[[2026,9,28]]}},"alternative-id":["10.1002\/cbic.70543"],"URL":"https:\/\/doi.org\/10.1002\/cbic.70543","archive":["Portico"],"relation":{},"ISSN":["1439-4227","1439-7633"],"issn-type":[{"value":"1439-4227","type":"print"},{"value":"1439-7633","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,20]]},"assertion":[{"value":"2026-07-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70543"}}