Conformational analysis of a potent SSTR3-selective somatostatin analogue by NMR in water solution.
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.
Gairí
Margarida
M
NMR Facility, Serveis Cientificotècnics, University of Barcelona, Barcelona Science Park, Josep Samitier 1-5, 08028 Barcelona, Spain.
Saiz
Pilar
P
Madurga
Sergio
S
Roig
Xavier
X
Erchegyi
Judit
J
Koerber
Steven C
SC
Reubi
Jean Claude
JC
Rivier
Jean E
JE
Giralt
Ernest
E
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
D017481:Receptors, Somatostatin; D012996:Solutions; C103631:somatostatin receptor 3; D014867:Water; D013004:Somatostatin