A bioactive somatostatin analog without a type II' beta-turn: synthesis and conformational analysis in solution

J Pept Sci. 2001 Oct;7(10):521-8. doi: 10.1002/psc.348.

Abstract

A cyclic somatostatin analog [structure: see text] (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' beta-turn. This is the first report of a potent bioactive somatostatin analog that does not exhibit a type II' beta-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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Humans
  • In Vitro Techniques
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Molecular Structure
  • Peptides, Cyclic / chemical synthesis*
  • Peptides, Cyclic / chemistry*
  • Peptides, Cyclic / metabolism
  • Protein Conformation
  • Protein Structure, Secondary
  • Receptors, Somatostatin / metabolism
  • Solutions
  • Somatostatin / analogs & derivatives*
  • Somatostatin / chemical synthesis
  • Somatostatin / chemistry
  • Somatostatin / metabolism
  • Thermodynamics

Substances

  • Peptides, Cyclic
  • Receptors, Somatostatin
  • Solutions
  • cysteinyl-phenylalanyl-tryptophyl-tryptophyl-lysyl-threonyl-phenylalanyl-N-ethylglycinamide cyclic (1-8-C2-ethyl)-disulfide
  • Somatostatin