Martín-Gago, PabloRol Rúa, ÁlvaroTodorovski, ToniAragón Altarriba, EricMartin-Malpartida, PauVerdaguer i Espaulella, XavierVallès Miret, MarionaFernández-Carneado, JimenaPonsati, BertaMacías Hernández, María J.Riera i Escalé, Antoni2016-09-092016-09-092016-06-072045-2322https://hdl.handle.net/2445/101682Somatostatin is a 14-residue peptide hormone that regulates the endocrine system by binding to five G-protein-coupled receptors (SSTR1-5). We have designed six new Somatostatin analogs with L-3-(3',5'-difluorophenyl)-alanine (Dfp) as a substitute of Phe and studied the effect of an electron-poor arom. ring in the network of arom. interactions present in Somatostatin. Replacement of each of the Phe residues (positions 6, 7 and 11) by Dfp and use of a D-Trp8 yielded peptides whose main conformations could be characterized in aq. soln. by NMR. Receptor binding studies revealed that the analog with Dfp at position 7 displayed a remarkable affinity to SSTR2 and SSTR3. Analogs with Dfp at positions 6 or 11 displayed a π-π interaction with the Phe present at 11 or 6, resp. Interestingly, these analogs, particularly [D-Trp8,L-Dfp11]-SRIF, showed high selectivity towards SSTR2, with a higher value than that of Octreotide and a similar one to that of native Somatostatin.9 p.application/pdfengcc-by-nc-nd (c) Martín-Gago, Pablo et al., 2016http://creativecommons.org/licenses/by-nc-nd/3.0/esPèptidsSomatostatinaHormones peptídiquesCompostos aromàticsPeptidesSomatostatinPeptide hormonesAromatic compoundsinfo:eu-repo/semantics/article6630232016-09-09info:eu-repo/semantics/openAccess27271737