title: Conformational analysis of a potent SSTR3-selective somatostatin analogue by NMR in water solution.
abstract: The three-dimensional structure of a potent SSTR3-selective analogue of somatostatin, cyclo(3-14)H-Cys(3)-Phe(6)-Tyr(7)-D-Agl(8)(N(beta) Me, 2-naphthoyl)-Lys(9)-Thr(10)-Phe(11)-Cys(14)-OH (des-AA(1, 2, 4, 5, 12, 13)[Tyr(7), D-Agl(8)(N(beta) Me, 2-naphthoyl)]-SRIF) (peptide 1) has been determined by (1)H NMR in water and molecular dynamics (MD) simulations. The peptide exists in two conformational isomers differing mainly by the cis/trans isomerization of the side chain in residue 8. The structure of 1 is compared with the consensus structural motifs of other somatostatin analogues that bind predominantly to SSTR1, SSTR2/SSTR5 and SSTR4 receptors, and to the 3D structure of a non-selective SRIF analogue, cyclo(3-14)H-Cys(3)-Phe(6)-Tyr(7)-D-2Nal(8)-Lys(9)-Thr(10)-Phe(11)-Cys(14)-OH (des-AA(1, 2, 4, 5, 12, 13)[Tyr(7), D-2Nal(8)]-SRIF) (peptide 2). The structural determinant factors that could explain selectivity of peptide 1 for SSTR3 receptors are discussed.
authors.affiliation: NMR Facility, Serveis Cientificotècnics, University of Barcelona, Barcelona Science Park, Josep Samitier 1-5, 08028 Barcelona, Spain.
authors.forename: Margarida
authors.initials: M
authors.lastname: Gairí
authors.forename: Pilar
authors.initials: P
authors.lastname: Saiz
authors.forename: Sergio
authors.initials: S
authors.lastname: Madurga
authors.forename: Xavier
authors.initials: X
authors.lastname: Roig
authors.forename: Judit
authors.initials: J
authors.lastname: Erchegyi
authors.forename: Steven C
authors.initials: SC
authors.lastname: Koerber
authors.forename: Jean Claude
authors.initials: JC
authors.lastname: Reubi
authors.forename: Jean E
authors.initials: JE
authors.lastname: Rivier
authors.forename: Ernest
authors.initials: E
authors.lastname: Giralt
mesh_terms: D000595:Amino Acid Sequence; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D011487:Protein Conformation; D017481:Receptors, Somatostatin / Q000737:chemistry*; D012996:Solutions; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000737:chemistry; D014867:Water
chemical_list: D017481:Receptors, Somatostatin; D012996:Solutions; C103631:somatostatin receptor 3; D014867:Water; D013004:Somatostatin