{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T16:25:17Z","timestamp":1787415917323,"version":"build-2736575974"},"reference-count":40,"publisher":"American Chemical Society (ACS)","issue":"33","license":[{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/na","name":"Characteristic Innovation Projects for Ordinary Universities of Guangdong Province","doi-asserted-by":"publisher","award":["2022KTSCX047"],"award-info":[{"award-number":["2022KTSCX047"]}],"id":[{"id":"10.13039\/na","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/na","name":"Characteristic Innovation Projects for Ordinary Universities of Guangdong Province","doi-asserted-by":"publisher","award":["2024KTSCX165"],"award-info":[{"award-number":["2024KTSCX165"]}],"id":[{"id":"10.13039\/na","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/na","name":"Guangdong Provincial Key Scientific Research Projects for Ordinary Higher Education Institutions","doi-asserted-by":"publisher","award":["2025ZDZX2024"],"award-info":[{"award-number":["2025ZDZX2024"]}],"id":[{"id":"10.13039\/na","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Peptide stapling exerts profound effects on key peptide properties, including metabolic stability, cell membrane permeability, and conformational constraint. Herein, we report a mild and efficient 2,4-dichloro-1,3,5-triazine-mediated stapling strategy for the selective cross-linking of lysine side-chain amines. This approach furnishes macrocyclic peptides of varying ring sizes. This method features broad functional group compatibility with most natural amino acid residues (His, Trp, Arg, Tyr, Ser and Thr), as well as N-terminal \u03b1-amino and C-terminal carboxylate moieties, whereas cysteine is not tolerated in this transformation. For the representative stapled macrocyclic peptides, the 1,3,5-triazine bridge significantly enhanced proteolytic stability, membrane permeability and helical propensity, and potentiated their antiproliferative activity against multiple cancer cell lines.<\/jats:p>","DOI":"10.1021\/acs.orglett.6c02701","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T15:01:52Z","timestamp":1786028512000},"page":"10457-10462","source":"Crossref","is-referenced-by-count":0,"title":["Triazine Linchpins\nfor Selective Lys-Lys Stapling\nof Unprotected Peptides"],"prefix":"10.1021","volume":"28","author":[{"given":"Peiru","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anhui","family":"Mao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingxiu","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yijing","family":"You","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingshi","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahao","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6980-1648","authenticated-orcid":true,"given":"Wenfang","family":"Xiong","sequence":"additional","affiliation":[{"name":"Guangdong Medical University , , ,","place":["Dongguan, China, 523808"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5821-703X","authenticated-orcid":true,"given":"Zunnan","family":"Huang","sequence":"additional","affiliation":[{"name":"Guangdong Medical University , , ,","place":["Dongguan, China, 523808"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0434-4711","authenticated-orcid":true,"given":"Jinwu","family":"Zhao","sequence":"additional","affiliation":[{"name":"Guangdong Medical University , , ,","place":["Dongguan, China, 523808"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,6]]},"reference":[{"issue":"5","key":"2026082212111255200_cit1a","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1038\/s41570-024-00591-5","article-title":"Non-symmetric stapling\nof native peptides","volume":"8","author":"Chen","year":"2024","journal-title":"Nat. Rev. Chem."},{"issue":"17","key":"2026082212111255200_cit1b","doi-asserted-by":"publisher","first-page":"9971","DOI":"10.1021\/acs.chemrev.8b00657","article-title":"Ligation Technologies\nfor the Synthesis of Cyclic Peptides","volume":"119","author":"Chow","year":"2019","journal-title":"Chem.\nRev."},{"issue":"24","key":"2026082212111255200_cit1c","doi-asserted-by":"publisher","first-page":"11725","DOI":"10.1039\/D3CS01066J","article-title":"C.-F. Recent\nadvances in peptide macrocyclization strategies","volume":"53","author":"Fang","year":"2024","journal-title":"Chem. Soc. Rev."},{"issue":"3","key":"2026082212111255200_cit1d","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202517565","article-title":"In Cellulo\nPeptide Cyclization via Gene-Encoded Proximity-Induced Proline-Isothiocyanate\nCrosslinking","volume":"65","author":"Huang","year":"2026","journal-title":"Angew. Chem., Int. Ed."},{"issue":"17","key":"2026082212111255200_cit1e","doi-asserted-by":"publisher","first-page":"9836","DOI":"10.1021\/acs.chemrev.8b00744","article-title":"Multicomponent Reaction\nToolbox for Peptide Macrocyclization and Stapling","volume":"119","author":"Reguera","year":"2019","journal-title":"Chem. Rev."},{"issue":"8","key":"2026082212111255200_cit1f","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202420522","article-title":"Tyrosinase-Catalyzed\nPeptide Stapling Using Para-Amino Phenylalanine and Tyrosine Anchoring\nResidues","volume":"64","author":"Wang","year":"2025","journal-title":"Angew. Chem., Int. Ed."},{"issue":"7","key":"2026082212111255200_cit1g","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1021\/cbe.3c00123","article-title":"Recent Advances in\nMetal-Free Peptide Stapling Strategies","volume":"1","author":"Zhan","year":"2024","journal-title":"Chem.\nBio. Eng."},{"issue":"17","key":"2026082212111255200_cit2a","doi-asserted-by":"publisher","first-page":"9743","DOI":"10.1021\/acs.chemrev.0c00013","article-title":"Strategies for Fine-Tuning\nthe Conformations of Cyclic Peptides","volume":"120","author":"Jwad","year":"2020","journal-title":"Chem.\nRev."},{"issue":"18","key":"2026082212111255200_cit2b","doi-asserted-by":"publisher","first-page":"10079","DOI":"10.1021\/acs.chemrev.0c00532","article-title":"Stapled Helical\nPeptides Bearing Different Anchoring Residues","volume":"120","author":"Li","year":"2020","journal-title":"Chem. Rev."},{"issue":"21","key":"2026082212111255200_cit2c","doi-asserted-by":"publisher","first-page":"2087","DOI":"10.1002\/cbic.201700352","article-title":"Effect of Stapling Architecture on Physiochemical Properties and\nCell Permeability of Stapled \u03b1-Helical Peptides: A Comparative\nStudy","volume":"18","author":"Tian","year":"2017","journal-title":"ChemBioChem."},{"issue":"33","key":"2026082212111255200_cit3a","doi-asserted-by":"publisher","first-page":"29930","DOI":"10.1021\/jacs.5c06944","article-title":"Intrastrand\nPeptide Staples That Promote \u03b2-Sheet Folding, Self-Assembly,\nand Amyloid Seeding","volume":"147","author":"Dangi","year":"2025","journal-title":"J. Am. Chem. Soc."},{"issue":"6","key":"2026082212111255200_cit3b","doi-asserted-by":"publisher","first-page":"843","DOI":"10.1002\/bip.22877","article-title":"Stapling peptides using cysteine crosslinking","volume":"106","author":"Fairlie","year":"2016","journal-title":"Pept. Sci."},{"issue":"11","key":"2026082212111255200_cit3c","doi-asserted-by":"publisher","first-page":"nwaf406","DOI":"10.1093\/nsr\/nwaf406","article-title":"Cys\u2013Lys stapling\nfor unprotected peptides via tunable linkers","volume":"12","author":"Miao","year":"2025","journal-title":"Natl. Sci. Rev."},{"issue":"2","key":"2026082212111255200_cit3d","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202518628","article-title":"Thiol\u2013Ene Photoclick\nChemistry for Efficient Bicyclic Peptide Synthesis and Genetically\nEncoded Peptide Library","volume":"65","author":"Ming","year":"2026","journal-title":"Angew. Chem., Int.\nEd."},{"issue":"31","key":"2026082212111255200_cit3e","doi-asserted-by":"publisher","first-page":"8597","DOI":"10.1021\/acs.orglett.5c02534","article-title":"Trifluoroacetic Acid\nPromotes Ultrafast Peptide Cyclization Mediated with Dimethylolurea","volume":"27","author":"Wang","year":"2025","journal-title":"Org. Lett."},{"issue":"5","key":"2026082212111255200_cit4a","doi-asserted-by":"publisher","first-page":"540","DOI":"10.37349\/eds.2024.00060","article-title":"Chemo-selective modification\nof cysteine\nresidue: synthesis and application in the discovery of potential drug\ncandidates","volume":"2","author":"Liao","year":"2024","journal-title":"Explor. Drug Sci."},{"issue":"2","key":"2026082212111255200_cit4b","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1021\/cb3005269","article-title":"Diverse Functional Roles of Reactive\nCysteines","volume":"8","author":"Pace","year":"2013","journal-title":"ACS Chem. Biol."},{"issue":"62","key":"2026082212111255200_cit5","doi-asserted-by":"publisher","DOI":"10.1002\/chem.202502273","article-title":"A General\nSynthesis Approach to Double-Guanidinium Stapled Peptides and Foldamers","volume":"31","author":"Neuville","year":"2025","journal-title":"Chem. \u2013 Eur. J."},{"issue":"27","key":"2026082212111255200_cit6","doi-asserted-by":"publisher","first-page":"8340","DOI":"10.1021\/jacs.6b03757","article-title":"Nitrogen\nArylation for Macrocyclization of Unprotected Peptides","volume":"138","author":"Lautrette","year":"2016","journal-title":"J. Am. Chem. Soc."},{"issue":"30","key":"2026082212111255200_cit7","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202405344","article-title":"Selective Macrocyclization\nof Unprotected Peptides with an Ex Situ Gaseous Linchpin Reagent","volume":"63","author":"Ding","year":"2024","journal-title":"Angew. Chem., Int. Ed."},{"issue":"1","key":"2026082212111255200_cit8","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1038\/s41467-022-27985-7","article-title":"Extendable\nstapling of unprotected peptides by crosslinking two amines with o-phthalaldehyde","volume":"13","author":"Li","year":"2022","journal-title":"Nat. Commun."},{"issue":"16","key":"2026082212111255200_cit9","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202318893","article-title":"Peptide Stapling\nby Crosslinking Two Amines with \u03b1-Ketoaldehydes through Diverse\nModified Glyoxal-Lysine Dimer Linkers","volume":"63","author":"Guo","year":"2024","journal-title":"Angew.\nChem., Int. Ed."},{"issue":"13","key":"2026082212111255200_cit10","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202422844","article-title":"Formamidine\nas an Easy-On and Easy-Off Linker for Reversible Crosslinking of Two\nAlkyl Amines in Peptide Stapling and Conjugation","volume":"64","author":"Chu","year":"2025","journal-title":"Angew. Chem., Int. Ed."},{"issue":"5","key":"2026082212111255200_cit11","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202416348","article-title":"Guanidinium-Stapled\nHelical Peptides for Targeting Protein-Protein Interactions","volume":"64","author":"Perdriau","year":"2025","journal-title":"Angew. Chem., Int. Ed."},{"issue":"51","key":"2026082212111255200_cit12","doi-asserted-by":"publisher","first-page":"14230","DOI":"10.1021\/acs.orglett.5c04412","article-title":"Synthesis of Bis-urea-Bridged\nCyclopeptides via Stapling of Unprotected\nPeptides","volume":"27","author":"Xiong","year":"2025","journal-title":"Org. Lett."},{"issue":"17","key":"2026082212111255200_cit13a","doi-asserted-by":"publisher","first-page":"10032","DOI":"10.1021\/acs.chemrev.8b00789","article-title":"Heteroaryl\nRings in Peptide Macrocycles","volume":"119","author":"Smolyar","year":"2019","journal-title":"Chem. Rev."},{"issue":"49","key":"2026082212111255200_cit13b","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aea6904","article-title":"Achieving cysteine-selective\npeptide\/protein bioconjugation via tunable triazine-pyridine chemistry","volume":"11","author":"Wang","year":"2025","journal-title":"Sci. Adv."},{"issue":"23","key":"2026082212111255200_cit13c","doi-asserted-by":"publisher","first-page":"25091","DOI":"10.1021\/acs.jmedchem.5c02059","article-title":"Conjugating 10,11-Dimethoxy-camptothecin with an Integrin\n\u03b1v\u03b23-Targeting Peptide through a Triazine Linker for Targeted\nTumor Treatment in Lung and Pancreatic Carcinoma","volume":"68","author":"Wang","year":"2025","journal-title":"J. Med. Chem."},{"issue":"2","key":"2026082212111255200_cit14","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1021\/jo005631q","article-title":"Sequential Nucleophilic\nSubstitution on Halogenated Triazines, Pyrimidines, and Purines: A\nNovel Approach to Cyclic Peptidomimetics","volume":"66","author":"Scharn","year":"2001","journal-title":"J.\nOrg. Chem."},{"issue":"19","key":"2026082212111255200_cit15","doi-asserted-by":"publisher","first-page":"5012","DOI":"10.1021\/ol201773f","article-title":"Design and Facile Solid-Phase Synthesis\nof Conformationally Constrained Bicyclic Peptoids","volume":"13","author":"Lee","year":"2011","journal-title":"Org. Lett."},{"issue":"64","key":"2026082212111255200_cit16","doi-asserted-by":"publisher","first-page":"9499","DOI":"10.1039\/C9CC05042F","article-title":"Macrocyclisation\nand functionalisation of unprotected peptides via divinyltriazine\ncysteine stapling","volume":"55","author":"Robertson","year":"2019","journal-title":"Chem. Commun."},{"issue":"12","key":"2026082212111255200_cit17","doi-asserted-by":"publisher","first-page":"4034","DOI":"10.1021\/ja512880g","article-title":"Peptide\/Protein Stapling and Unstapling:\nIntroduction of s-Tetrazine, Photochemical Release, and Regeneration\nof the Peptide\/Protein","volume":"137","author":"Brown","year":"2015","journal-title":"J. Am. Chem. Soc."},{"issue":"13","key":"2026082212111255200_cit18","doi-asserted-by":"publisher","first-page":"2248","DOI":"10.1021\/acs.orglett.3c00499","article-title":"Peptide Stapling\nthrough Site-Directed Conjugation of Triazine Moieties to the Tyrosine\nResidues of a Peptide","volume":"25","author":"Zhang","year":"2023","journal-title":"Org. Lett."},{"issue":"1","key":"2026082212111255200_cit19","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1515\/epoly-2022-0012","article-title":"Study on the\nself-assembly of aromatic antimicrobial peptides based on different\nPAF26 peptide sequences","volume":"22","author":"Cao","year":"2022","journal-title":"e-Polym."},{"key":"2026082212111255200_cit20","doi-asserted-by":"publisher","first-page":"405","DOI":"10.3389\/fchem.2020.00405","article-title":"A rapid and\nefficient building block approach for click cyclization of peptoids","volume":"8","author":"Samarasimhareddy","year":"2020","journal-title":"Front. Chem."},{"issue":"1","key":"2026082212111255200_cit21","doi-asserted-by":"publisher","first-page":"4529","DOI":"10.1038\/s41598-024-55205-3","article-title":"Novel antimicrobial peptides against\nCutibacterium acnes designed\nby deep learning","volume":"14","author":"Dong","year":"2024","journal-title":"Sci. Rep."},{"issue":"41","key":"2026082212111255200_cit22a","doi-asserted-by":"publisher","first-page":"16374","DOI":"10.1021\/jacs.9b07578","article-title":"Versatile\nPeptide Macrocyclization with Diels-Alder\nCycloadditions","volume":"141","author":"Montgomery","year":"2019","journal-title":"J. Am. Chem. Soc."},{"issue":"51","key":"2026082212111255200_cit22b","doi-asserted-by":"publisher","first-page":"23614","DOI":"10.1021\/jacs.2c10949","article-title":"Customized reversible stapling for selective delivery of bioactive\npeptides","volume":"144","author":"Zeng","year":"2022","journal-title":"J. Am. Chem. Soc."},{"issue":"9","key":"2026082212111255200_cit23a","doi-asserted-by":"publisher","first-page":"2456","DOI":"10.1021\/ja0693587","article-title":"Reactivation of the p53 tumor suppressor\npathway by a stapled p53 peptide","volume":"129","author":"Bernal","year":"2007","journal-title":"J. Am. Chem.\nSoc."},{"key":"2026082212111255200_cit23b","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1016\/j.ccr.2010.10.024","article-title":"A Stapled p53 Helix\nOvercomes HDMX-Mediated Suppression of p53","volume":"18","author":"Bernal","year":"2010","journal-title":"Cancer cell"}],"container-title":["Organic Letters"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.orglett.6c02701","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/orlef7\/article-pdf\/28\/33\/10457\/66447138\/acs.orglett.6c02701.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/orlef7\/article-pdf\/28\/33\/10457\/66447138\/acs.orglett.6c02701.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T16:11:19Z","timestamp":1787415079000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/orlef7\/article\/28\/33\/10457\/5249641\/Triazine-Linchpins-for-Selective-Lys-Lys-Stapling"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,6]]},"references-count":40,"journal-issue":{"issue":"33","published-online":{"date-parts":[[2026,8,6]]},"published-print":{"date-parts":[[2026,8,21]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.orglett.6c02701","relation":{},"ISSN":["1523-7060","1523-7052"],"issn-type":[{"value":"1523-7060","type":"print"},{"value":"1523-7052","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,6]]}}}