title: A tetradecapeptide somatostatin dicarba-analog: Synthesis, structural impact and biological activity.
abstract: We described here the first tetradecapeptide somatostatin-analogue where the disulfide bridge has been replaced by a carbon-carbon double bond. This analogue was prepared using microwave assisted ring closing metathesis (RCM) using the 2nd generation Grubbs as catalyst. Under our optimized conditions the cyclization between allylGly 3 and 14 proceeded in moderate yield, excellent cyclic/linear ratio and very high Z-double bond selectivity. NMR studies also demonstrated that the conformational flexibility of this peptide is increased in comparison to that of the natural hormone. Remarkably, this alkene-bridged somatostatin analog is highly selective against somatostatin receptors 1 and 5, suggesting that conformational rigidity is not required for the efficient interaction of somatostatin analogues with these two receptors.
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), Baldiri Reixac, 10, 08028 Barcelona, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Martín-Gago
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), Baldiri Reixac, 10, 08028 Barcelona, Spain; Departament de Química Orgànica, Universitat de Barcelona, Martí i Franqués, 1-11, 08028 Barcelona, Spain.
authors.forename: Rosario
authors.initials: R
authors.lastname: Ramón
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), Baldiri Reixac, 10, 08028 Barcelona, Spain.
authors.forename: Eric
authors.initials: E
authors.lastname: Aragón
authors.affiliation: BCN Peptides S.A. Pol.Ind. Els Vinyets-Els Fogars, Sector II. Ctra. Comarcal 244, Km. 22. Sant Quintí de Mediona, 08777 Barcelona, Spain.
authors.forename: Jimena
authors.initials: J
authors.lastname: Fernández-Carneado
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), Baldiri Reixac, 10, 08028 Barcelona, Spain.
authors.forename: Pau
authors.initials: P
authors.lastname: Martin-Malpartida
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), Baldiri Reixac, 10, 08028 Barcelona, Spain; Departament de Química Orgànica, Universitat de Barcelona, Martí i Franqués, 1-11, 08028 Barcelona, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Verdaguer
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Alcalá de Henares, 28871 Madrid, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: López-Ruiz
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Alcalá de Henares, 28871 Madrid, Spain.
authors.forename: Begoña
authors.initials: B
authors.lastname: Colás
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Alcalá de Henares, 28871 Madrid, Spain.
authors.forename: María Alicia
authors.initials: MA
authors.lastname: Cortes
authors.affiliation: BCN Peptides S.A. Pol.Ind. Els Vinyets-Els Fogars, Sector II. Ctra. Comarcal 244, Km. 22. Sant Quintí de Mediona, 08777 Barcelona, Spain.
authors.forename: Berta
authors.initials: B
authors.lastname: Ponsati
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), Baldiri Reixac, 10, 08028 Barcelona, Spain; Institució Catalana de Recerca i Estudis Avançats (ICREA), Passeig Lluis Companys, 23, 08010 Barcelona, Spain. Electronic address: maria.macias@irbbarcelona.org.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Macias
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), Baldiri Reixac, 10, 08028 Barcelona, Spain; Departament de Química Orgànica, Universitat de Barcelona, Martí i Franqués, 1-11, 08028 Barcelona, Spain. Electronic address: antoni.riera@irbbarcelona.org.
authors.forename: Antoni
authors.initials: A
authors.lastname: Riera
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D008872:Microwaves; D015394:Molecular Structure; D051381:Rats; D017481:Receptors, Somatostatin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D017481:Receptors, Somatostatin; D013004:Somatostatin
keywords: NMR studies; Peptide analogs; Ring-closing metathesis; Somatostatin