Título:
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Two-electron connection between tryptophan and phenylalanine/tyrosine residues: linked, constrained and stapled peptides through C-H activation processes
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Autor/a:
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Mendive Tapia, Lorena; Preciado Gallego, Sara; García, Jesús; Ramón, Rosario; Kielland, Nicola; Albericio Palomera, Fernando; Lavilla Grífols, Rodolfo
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Otros autores:
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Universitat de Barcelona |
Abstract:
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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. |
Materia(s):
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-Síntesi en fase sólida -Química combinatòria -Ressonància magnètica nuclear -Solid-phase synthesis -Combinatorial chemistry -Nuclear magnetic resonance |
Derechos:
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cc-by (c) Mendive Tapia, Lorena et al., 2015
http://creativecommons.org/licenses/by/3.0/es |
Tipo de documento:
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Artículo Artículo - Versión publicada |
Editor:
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Nature Publishing Group
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Compartir:
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