title: Discovery of iodinated somatostatin analogues selective for hsst2 and hsst5 with excellent inhibition of growth hormone and prolactin release from rat pituitary cells.
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.
authors.affiliation: University of California-San Diego, 9500 Gilman Drive, La Jolla, California 92093-0343, and Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Sandra Blaj
authors.initials: SB
authors.lastname: Moore
authors.forename: Joost
authors.initials: J
authors.lastname: van der Hoek
authors.forename: Antonia
authors.initials: A
authors.lastname: de Capua
authors.forename: Peter M
authors.initials: PM
authors.lastname: van Koetsveld
authors.forename: Leo J
authors.initials: LJ
authors.lastname: Hofland
authors.forename: Steven W J
authors.initials: SW
authors.lastname: Lamberts
authors.forename: Murray
authors.initials: M
authors.lastname: Goodman
mesh_terms: D015082:2,2'-Dipyridyl / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D005260:Female; D013006:Growth Hormone / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D050607:Organogold Compounds / Q000737:chemistry / Q000494:pharmacology*; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000494:pharmacology; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011388:Prolactin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D017481:Receptors, Somatostatin / Q000378:metabolism*; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: C505977:(4-amino-3-iodo)phenylalanyl-cyclo(cysteinyl-tyrosyl-tryptophyl-lysyl-valyl-cysteinyl)threoninamide; D050607:Organogold Compounds; D010456:Peptides, Cyclic; D017481:Receptors, Somatostatin; C453480:hydroxo(6-(1,1-dimethylbenzyl)-2,2'-bipyridine)gold(III); D013004:Somatostatin; D015082:2,2'-Dipyridyl; C094573:somatostatin receptor 5; D011388:Prolactin; D013006:Growth Hormone; C093733:somatostatin receptor 2; C505978:AP-102