title: A new peptidic somatostatin agonist with high affinity to all five somatostatin receptors.
abstract: All commercially available somatostatin analogs for clinical use have a preference for some but not all somatostatin receptor subtypes. We describe here the synthesis and evaluation in binding and cAMP assays with cell lines stably transfected with sst(1)-sst(5) of a new type of nonapeptide somatostatin analog with a reduced-sized and stabilized structure, Tyr(0)-(cyclo-D-Dab-Arg-Phe-Phe-D-Trp-Lys-Thr-Phe) (KE108). All five somatostatin receptors subtypes have an extremely high affinity for KE108, equivalent to SS-28 at sst(1) and two to four times higher than SS-28 at sst(2), sst(3), sst(4) and sst(5). Moreover, the compound has agonistic properties at all five subtypes, since it is able to inhibit the forskolin-stimulated cAMP production in sst(1)-sst(5) cells. It is stable for several hours in human serum. This analog may therefore represent a considerable improvement over commercially available somatostatin analogs as it will target all somatostatin receptor subtypes, a particular advantage for cancer-related applications, as human cancers can express concomitantly several somatostatin receptor subtypes.
authors.affiliation: Division of Cell Biology and Experimental Cancer Research, Institute of Pathology, University of Berne, Switzerland. reubi@pathology.unibe.ch
authors.forename: Jean Claude
authors.initials: JC
authors.lastname: Reubi
authors.forename: Klaus-Peter
authors.initials: KP
authors.lastname: Eisenwiener
authors.forename: Hans
authors.initials: H
authors.lastname: Rink
authors.forename: Beatrice
authors.initials: B
authors.lastname: Waser
authors.forename: Helmut R
authors.initials: HR
authors.lastname: Mäcke
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D016466:CHO Cells; D002460:Cell Line; D005576:Colforsin / Q000494:pharmacology; D006224:Cricetinae; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D009842:Oligopeptides / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D020033:Protein Isoforms / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D017481:Receptors, Somatostatin / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D013004:Somatostatin / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D014162:Transfection
chemical_list: D009842:Oligopeptides; D010456:Peptides, Cyclic; D020033:Protein Isoforms; D017481:Receptors, Somatostatin; C473958:Tyr(0)-(cyclo-D-Dab-Arg-Phe-Phe-D-Trp-Lys-Thr-Phe); D005576:Colforsin; D013004:Somatostatin; D000242:Cyclic AMP