{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T19:40:41Z","timestamp":1767987641562,"version":"3.49.0"},"reference-count":12,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,9,8]],"date-time":"2023-09-08T00:00:00Z","timestamp":1694131200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Nambiosis-CIBER BBN, Peptide Synthesis Unit (U3)","award":["1210056"],"award-info":[{"award-number":["1210056"]}]},{"name":"Nambiosis-CIBER BBN, Peptide Synthesis Unit (U3)","award":["21191601"],"award-info":[{"award-number":["21191601"]}]},{"name":"Fondecyt Regular","award":["1210056"],"award-info":[{"award-number":["1210056"]}]},{"name":"Fondecyt Regular","award":["21191601"],"award-info":[{"award-number":["21191601"]}]},{"name":"Beca Doctorado ANID","award":["1210056"],"award-info":[{"award-number":["1210056"]}]},{"name":"Beca Doctorado ANID","award":["21191601"],"award-info":[{"award-number":["21191601"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MPs"],"abstract":"<jats:p>Used in solid-phase peptide synthesis (SPPS) for peptides with an acid termination, the 2-chlorotrityl chloride (2-CTC) resin is highly susceptible to moisture, leading to reduced resin loading and lower synthetic yields. It is therefore recommended that the resin be activated with thionyl chloride (SOCl2) before peptide assembly. Here we present an optimized procedure for resin activation that minimizes the use of SOCl2 as the activation reagent and reduces the activation time. Additionally, we demonstrate the feasibility of reusing the 2-CTC resin when following the activation protocol, achieving comparable results to the first usage of the resin. Moreover, we achieved different degrees of resin activation by varying the amount of SOCl2. For instance, the use of 2% SOCl2 in anhydrous dichloromethane (DCM) allowed up to 44% activation of the resin, thereby making it suitable for the synthesis of longer peptides. Alternatively, employing 25% SOCl2 in anhydrous DCM resulted in up to 80% activation with a reaction time of only 5 min in both cases.<\/jats:p>","DOI":"10.3390\/mps6050082","type":"journal-article","created":{"date-parts":[[2023,9,8]],"date-time":"2023-09-08T08:01:30Z","timestamp":1694160090000},"page":"82","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Improving 2-Chlorotrityl Chloride (2-CTC) Resin Activation"],"prefix":"10.3390","volume":"6","author":[{"given":"Tanya","family":"Rom\u00e1n","sequence":"first","affiliation":[{"name":"N\u00facleo Biotecnolog\u00eda Curauma, Pontificia Universidad Cat\u00f3lica de Valpara\u00edso, Valpara\u00edso 2373223, Chile"},{"name":"Doctorado en Biotecnolog\u00eda, Pontificia Universidad Cat\u00f3lica de Valpara\u00edso, Universidad T\u00e9cnica Federico Santa Mar\u00eda, Valpara\u00edso 2373223, Chile"},{"name":"Department of Organic Chemistry and CIBER-BBN, Networking Centre on Bioengineering, Biomaterials and Nanomedicine, University of Barcelona, 08028 Barcelona, Spain"},{"name":"Institute for Advanced Chemistry of Catalonia (IQAC-CSIC), Jordi Girona 18-26, 08034 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerardo","family":"Acosta","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry and CIBER-BBN, Networking Centre on Bioengineering, Biomaterials and Nanomedicine, University of Barcelona, 08028 Barcelona, Spain"},{"name":"Institute for Advanced Chemistry of Catalonia (IQAC-CSIC), Jordi Girona 18-26, 08034 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8521-9172","authenticated-orcid":false,"given":"Beatriz G.","family":"de la Torre","sequence":"additional","affiliation":[{"name":"KwaZulu-Natal Research Innovation and Sequencing Platform (KRISP), School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban 4041, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3673-9320","authenticated-orcid":false,"given":"Constanza","family":"C\u00e1rdenas","sequence":"additional","affiliation":[{"name":"N\u00facleo Biotecnolog\u00eda Curauma, Pontificia Universidad Cat\u00f3lica de Valpara\u00edso, Valpara\u00edso 2373223, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7829-0568","authenticated-orcid":false,"given":"Fanny","family":"Guzm\u00e1n","sequence":"additional","affiliation":[{"name":"N\u00facleo Biotecnolog\u00eda Curauma, Pontificia Universidad Cat\u00f3lica de Valpara\u00edso, Valpara\u00edso 2373223, Chile"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8946-0462","authenticated-orcid":false,"given":"Fernando","family":"Albericio","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry and CIBER-BBN, Networking Centre on Bioengineering, Biomaterials and Nanomedicine, University of Barcelona, 08028 Barcelona, Spain"},{"name":"Institute for Advanced Chemistry of Catalonia (IQAC-CSIC), Jordi Girona 18-26, 08034 Barcelona, Spain"},{"name":"Peptide Science Laboratory, School of Chemistry and Physics, University of KwaZulu-Natal, Westville, Durban 4000, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1002\/qsar.200720015","article-title":"Chlorotrityl Chloride (CTC) Resin as a Reusable Carboxyl Protecting Group","volume":"26","author":"Cruz","year":"2007","journal-title":"QSAR Comb. Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1039\/C8RE00318A","article-title":"A Continuous Flow Protocol to Generate, Regenerate, Load, and Recycle Chlorotrityl Functionalised Resins","volume":"4","author":"Spare","year":"2019","journal-title":"React. Chem. Eng."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2165","DOI":"10.1021\/acs.jnatprod.1c00222","article-title":"The Total Chemical Synthesis and Biological Evaluation of the Cationic Antimicrobial Peptides, Laterocidine and Brevicidine","volume":"84","author":"Hermant","year":"2021","journal-title":"J. Nat. Prod."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1934","DOI":"10.1002\/adsc.202200079","article-title":"Recent Progress in Solid-Phase Total Synthesis of Naturally Occurring Small Peptides","volume":"364","author":"Yan","year":"2022","journal-title":"Adv. Synth. Catal."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2685","DOI":"10.1021\/acs.bioconjchem.0c00563","article-title":"Rapid, High-Yielding Solid-Phase Synthesis of Cathepsin-B Cleavable Linkers for Targeted Cancer Therapeutics","volume":"31","author":"Pryyma","year":"2020","journal-title":"Bioconjug. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"447","DOI":"10.3389\/fchem.2020.00447","article-title":"Methodologies for Backbone Macrocyclic Peptide Synthesis Compatible with Screening Technologies","volume":"8","author":"Shinbara","year":"2020","journal-title":"Front. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"8466","DOI":"10.1002\/ange.202012643","article-title":"Connecting Hydrophobic Surfaces in Cyclic Peptides Increases Membrane Permeability","volume":"133","author":"Hoang","year":"2021","journal-title":"Angew. Chemie"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.1002\/chem.201905385","article-title":"Cyclic Peptides as Drugs for Intracellular Targets: The Next Frontier in Peptide Therapeutic Development","volume":"27","author":"Buckton","year":"2021","journal-title":"Chem.\u2014A Eur. J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1021\/acs.oprd.9b00073","article-title":"Troubleshooting When Using \u03b3-Valerolactone (GVL) in Green Solid-Phase Peptide Synthesis","volume":"23","author":"Kumar","year":"2019","journal-title":"Org. Process Res. Dev."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1038\/s41573-020-00135-8","article-title":"Trends in Peptide Drug Discovery","volume":"20","author":"Muttenthaler","year":"2021","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1021\/cc7001588","article-title":"Cysteine- S -Trityl a Key Derivative to Prepare N-Methyl Cysteines","volume":"10","author":"Marcucci","year":"2008","journal-title":"J. Comb. Chem."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1450","DOI":"10.1021\/acs.oprd.2c00052","article-title":"Missing Link: Enabling Loading of 2-Chlorotrityl Chloride Resin in N-Butylpyrrolidinone as a Green Solvent","volume":"26","author":"Lopez","year":"2022","journal-title":"Org. Process Res. Dev."}],"container-title":["Methods and Protocols"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2409-9279\/6\/5\/82\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:47:18Z","timestamp":1760129238000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2409-9279\/6\/5\/82"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,8]]},"references-count":12,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2023,10]]}},"alternative-id":["mps6050082"],"URL":"https:\/\/doi.org\/10.3390\/mps6050082","relation":{},"ISSN":["2409-9279"],"issn-type":[{"value":"2409-9279","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,8]]}}}