2026-04-13T14:19:19Zhttps://recercat.cat/oai/request

oai:recercat.cat:2445/1327172025-12-04T21:44:01Zcom_2072_1057col_2072_478917col_2072_478933

00925njm 22002777a 4500 dc Mendive Tapia, Lorena author Preciado Gallego, Sara author García, Jesús author Ramón, Rosario author Kielland, Nicola author Albericio Palomera, Fernando author Lavilla Grífols, Rodolfo author 2019-05-06T09:46:47Z 2019-05-06T09:46:47Z 2015-05-21 2019-05-06T09:46:48Z Natural 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. Síntesi en fase sólida Química combinatòria Ressonància magnètica nuclear Solid-phase synthesis Combinatorial chemistry Nuclear magnetic resonance Two-electron connection between tryptophan and phenylalanine/tyrosine residues: linked, constrained and stapled peptides through C-H activation processes