title: New peptide architectures through C-H activation stapling between tryptophan-phenylalanine/tyrosine residues.
abstract: 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.
authors.affiliation: 1] Institute for Research in Biomedicine, Barcelona Science Park, Baldiri Reixac 10-12, 08028 Barcelona, Spain [2] Department of Organic Chemistry, University of Barcelona, Martí i Franqués 1-11, 08028 Barcelona, Spain [3] CIBER-BBN, Networking Centre on Bioengineering, Biomaterials and Nanomedicine.
authors.forename: Lorena
authors.initials: L
authors.lastname: Mendive-Tapia
authors.affiliation: Department of Organic Chemistry, University of Barcelona, Martí i Franqués 1-11, 08028 Barcelona, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Preciado
authors.affiliation: Institute for Research in Biomedicine, Barcelona Science Park, Baldiri Reixac 10-12, 08028 Barcelona, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: García
authors.affiliation: Barcelona Science Park, Baldiri Reixac 10-12, 08028 Barcelona, Spain.
authors.forename: Rosario
authors.initials: R
authors.lastname: Ramón
authors.affiliation: Barcelona Science Park, Baldiri Reixac 10-12, 08028 Barcelona, Spain.
authors.forename: Nicola
authors.initials: N
authors.lastname: Kielland
authors.affiliation: 1] Institute for Research in Biomedicine, Barcelona Science Park, Baldiri Reixac 10-12, 08028 Barcelona, Spain [2] Department of Organic Chemistry, University of Barcelona, Martí i Franqués 1-11, 08028 Barcelona, Spain [3] CIBER-BBN, Networking Centre on Bioengineering, Biomaterials and Nanomedicine [4] School of Chemistry, Yachay Tech, Yachay City of Knowledge, 100119 Urcuqui, Ecuador.
authors.forename: Fernando
authors.initials: F
authors.lastname: Albericio
authors.affiliation: 1] Barcelona Science Park, Baldiri Reixac 10-12, 08028 Barcelona, Spain [2] Laboratory of Organic Chemistry, Faculty of Pharmacy, University of Barcelona, Avda. Joan XXII s.n., 08028 Barcelona, Spain.
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Lavilla
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D060326:Chemistry Techniques, Synthetic; D010455:Peptides / Q000138:chemical synthesis*
chemical_list: D000596:Amino Acids; D010455:Peptides