Mendive Tapia, LorenaPreciado Gallego, SaraGarcía, JesúsRamón, RosarioKielland, NicolaAlbericio Palomera, FernandoLavilla Grífols, Rodolfo2019-05-062019-05-062015-05-212041-1723https://hdl.handle.net/2445/132717Natural peptides show high degrees of specificity in their biological action. However, their therapeutical profile is severely limited by their conformational freedom and metabolic instability. Stapled peptides constitute a solution to these problems and access to these structures lies on a limited number of reactions involving the use of non-natural amino acids. Here, we describe a synthetic strategy for the preparation of unique constrained peptides featuring a covalent bond between tryptophan and phenylalanine or tyrosine residues. The preparation of such peptides is achieved in solution and on solid phase directly from the corresponding sequences having an iodo-aryl amino acid through an intramolecular palladium-catalysed C-H activation process. Moreover, complex topologies arise from the internal stapling of cyclopeptides and double intramolecular arylations within a linear peptide. Finally, as a proof of principle, we report the application to this new stapling method to relevant biologically active compounds.application/pdfengcc-by (c) Mendive Tapia, Lorena et al., 2015http://creativecommons.org/licenses/by/3.0/esSíntesi en fase sólidaQuímica combinatòriaRessonància magnètica nuclearSolid-phase synthesisCombinatorial chemistryNuclear magnetic resonanceinfo:eu-repo/semantics/article6670162019-05-06info:eu-repo/semantics/openAccess