biostudies-literatureN'dri OSLNatural Sciences and Engineering Research Council of CanadaFonds de Recherche du Québec-Nature et Technologie for support of the Biodiversa+ programCentre in Green Chemistry and CatalysisCIHRe70068https://www.ebi.ac.uk/biostudies/studies/S-EPMC12714488biostudies-literatureUnknown32(2)The constrained tryptophan (Trp) analog 1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid (Tcc) is used to restrict peptide conformation in structure-activity relationship studies. Although Pictet-Spengler cyclization of Trp and aldehydes with mineral acid gives Tcc analogs, such harsh conditions do not tolerate acid-labile functionality. To enable broader use of Tcc residues, mild conditions are now reported for the on-resin Pictet-Spengler cyclisation in the presence of acid-labile side chain protection and linker strategies.Journal of peptide science : an official publication of the European Peptide SocietyOn-Resin Pictet-Spengler Cyclization for 1,2,3,4-Tetrahydro-β-carboline-3-carboxylate (Tcc) Peptide Synthesis With Acid-Labile Functional Tolerance.PMC12714488PJT-186296CGCC, FRQNT-2020-RS4-265155-CCVCRGPIN-2025-04423356910Sadanandhan CPMaclean WBhowal KBWei XTruong DDif-Yaiche LLubell WDN'dri OSLYongo-Luwawa CDBoccino IVilleneuve ZfalseOn-Resin Pictet-Spengler Cyclization for 1,2,3,4-Tetrahydro-β-carboline-3-carboxylate (Tcc) Peptide Synthesis With Acid-Labile Functional Tolerance.The constrained tryptophan (Trp) analog 1,2,3,4-tetrahydro-β-carboline-3-carboxylic acid (Tcc) is used to restrict peptide conformation in structure-activity relationship studies. Although Pictet-Spengler cyclization of Trp and aldehydes with mineral acid gives Tcc analogs, such harsh conditions do not tolerate acid-labile functionality. To enable broader use of Tcc residues, mild conditions are now reported for the on-resin Pictet-Spengler cyclisation in the presence of acid-labile side chain protection and linker strategies.2026-01-01T00:00:00Z2026 Feb2026-06-06T05:38:55.125Z2026-05-26T03:12:22.707ZS-EPMC127144884141255810.1002/psc.70068