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‐Cys3‐Phe6‐Tyr7‐D‐Agl8(Nβ Me, 2‐naphthoyl)‐Lys9‐Thr10‐Phe11‐Cys14‐OH (des‐AA1, 2, 4, 5, 12, 13[Tyr7, D‐Agl8(Nβ Me, 2‐naphthoyl)]‐SRIF) (peptide 1) has been determined by 1H 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‐Cys3‐Phe6‐Tyr7‐D‐2Nal8‐Lys9‐Thr10‐Phe11‐Cys14‐OH (des‐AA1, 2, 4, 5, 12, 13[Tyr7, D‐2Nal8]‐SRIF) (peptide 2). The structural determinant factors that could explain selectivity of peptide 1 for SSTR3 receptors are discussed. Copyright © 2005 European Peptide Society and John Wiley & Sons, Ltd.