A bioactive somatostatin analog without a type II′ β-turn: Synthesis and conformational analysis in solution

Shaokai Jiang, Sharon Gazal, Gary Gelerman, Ofer Ziv, Olga Karpov, Pninit Litman, Moshe Bracha, Michael Afargan, Chaim Gilon, Murray Goodman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

A cyclic somatostatin analog S-S-[CH2]2 (1) has been synthesized. Biological assays show that this compound has strong binding affinities to somatostatin hsst2 and hsst5 receptor subtypes (5.2 and 1.2 nM, respectively, and modest affinity to hsst4 (41.1 nM)). Our conformational analysis carried out in DMSO-d6 indicates that this compound exists as two structures arising from the trans and cis configurations of the peptide bond between Phe7 and N-alkylated Gly8. However, neither conformer exhibits a type II′ β-turn. This is the first report of a potent bioactive somatostatin analog that does not exhibit a type II′ β-turn in solution. Molecular dynamics simulations (500 ps) carried out at 300 K indicate that the backbone of compound 1 is more flexible than other cyclic somatostatin analogs formed by disulfide bonds.

Original languageEnglish
Pages (from-to)521-528
Number of pages8
JournalJournal of Peptide Science
Volume7
Issue number10
DOIs
StatePublished - 2001

Keywords

  • β-turn
  • Conformation
  • NMR
  • Somatostatin

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