Conformational analysis of a potent SSTR3-selective somatostatin analogue by NMR in water solution

✍ Scribed by Margarida Gairí; Pilar Saiz; Sergio Madurga; Xavier Roig; Judit Erchegyi; Steven C. Koerber; Jean Claude Reubi; Jean E. Rivier; Ernest Giralt

• Book ID: 105360564
• Publisher: John Wiley and Sons
• Year: 2006
• Tongue: English
• Weight: 286 KB
• Volume: 12
• Category: Article
• ISSN: 1075-2617
• DOI: 10.1002/psc.743

✦ Synopsis

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^β^ 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^β^ 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. Copyright © 2005 European Peptide Society and John Wiley & Sons, Ltd.