New sst4/5-selective somatostatin peptidomimetics based on a constrained tryptophan scaffold

J Med Chem. 2007 Jul 12;50(14):3397-401. doi: 10.1021/jm070246f. Epub 2007 Jun 9.

Abstract

The synthesis and biological evaluation of four peptidomimetic analogs of somatostatin based on a constrained Trp residue, 3-amino-indolo[2,3-c]azepin-2-one (Aia), are reported. It is shown that dipeptidomimetics with a D-Aia-Lys sequence, functionalized with N- and C-terminal aromatic substituents, display a good selectivity for both sst4 and sst5. This study allowed us to identify a new highly potent sst5 agonist with good selectivity over the other receptors, except versus sst4.

MeSH terms

  • Animals
  • CHO Cells
  • Cricetinae
  • Cricetulus
  • Cyclic AMP / biosynthesis
  • Molecular Conformation
  • Molecular Mimicry*
  • Nuclear Magnetic Resonance, Biomolecular
  • Somatostatin / chemistry*
  • Tryptophan / chemistry*

Substances

  • Somatostatin
  • Tryptophan
  • Cyclic AMP