Discovery of iodinated somatostatin analogues selective for hsst2 and hsst5 with excellent inhibition of growth hormone and prolactin release from rat pituitary cells

J Med Chem. 2005 Oct 20;48(21):6643-52. doi: 10.1021/jm050376t.

Abstract

Inhibition of growth hormone (GH) and prolactin (PRL) release from the anterior pituitary gland is mediated through somatostatin receptor subtypes sst2 and sst5. It has been found that somatostatin (SS) analogues that are selective for both receptor subtypes are more effective at inhibiting GH and PRL release than monospecific analogues alone. We synthesized several disulfide-bridged octapeptide SS analogues. Iodinated compounds 7, (4-amino-3-iodo)-d-Phe-c[Cys-Tyr-d-Trp-Lys-Val-Cys]-Thr-NH2, and 9, (4-amino-3-iodo)-d-Phe-c[Cys-(3-iodo)-Tyr-d-Trp-Lys-Val-Cys]-Thr-NH2, were as potent as somatostatin in binding at receptors hsst2 and hsst5 and inhibited GH and PRL release from rat pituitary cells as potently as somatostatin.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 2,2'-Dipyridyl / analogs & derivatives*
  • 2,2'-Dipyridyl / chemistry
  • 2,2'-Dipyridyl / pharmacology
  • Animals
  • Cell Line
  • Cricetinae
  • Cricetulus
  • Female
  • Growth Hormone / antagonists & inhibitors*
  • Growth Hormone / metabolism
  • Humans
  • In Vitro Techniques
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Molecular Conformation
  • Organogold Compounds / chemistry
  • Organogold Compounds / pharmacology*
  • Peptides, Cyclic / chemical synthesis*
  • Peptides, Cyclic / pharmacology
  • Pituitary Gland, Anterior / cytology
  • Pituitary Gland, Anterior / drug effects*
  • Pituitary Gland, Anterior / metabolism
  • Prolactin / antagonists & inhibitors*
  • Prolactin / metabolism
  • Radioligand Assay
  • Rats
  • Receptors, Somatostatin / metabolism*
  • Somatostatin / analogs & derivatives*
  • Somatostatin / chemical synthesis*
  • Somatostatin / pharmacology
  • Structure-Activity Relationship

Substances

  • (4-amino-3-iodo)phenylalanyl-cyclo(cysteinyl-tyrosyl-tryptophyl-lysyl-valyl-cysteinyl)threoninamide
  • Organogold Compounds
  • Peptides, Cyclic
  • Receptors, Somatostatin
  • hydroxo(6-(1,1-dimethylbenzyl)-2,2'-bipyridine)gold(III)
  • Somatostatin
  • 2,2'-Dipyridyl
  • somatostatin receptor 5
  • Prolactin
  • Growth Hormone
  • somatostatin receptor 2
  • AP-102