title: The enantiomer of octreotate binds to all five somatostatin receptors with almost equal micromolar affinity--a comparison with SANDOSTATIN.
abstract: Octreotate (1b) is the octreotide (SANDOSTATIN; 1a) analogue, carrying a C-terminal CO(2)H (Thr) instead of the CH(2)OH (threoninol) group. In pursuit of our interest in unnatural peptides, we have now synthesized (by the solid-phase Fmoc method) the enantiomeric form 2 of octreotate and determined its affinity for the five human somatostatin (SRIF) receptors (hsst(1-5)). The binding was found to be 9.1, 4.1, 1.0, 1.4, and 4.2 microM, respectively. This almost equal one-digit micromolar affinity of ent-octreotate (2) to all five receptors contrasts with the behavior of most other somatostatin mimics including SANDOSTATIN (octreotide; 1a) and [Tyr(3)]-octreotate (1c), which have affinities for the various receptors differing up to and above 10(4)-fold. Thus, the structure of the new compound does not prevent binding, albeit more weakly than its pseudo-enantiomer octreotide, and there is hardly any selectivity of the peptide-protein interaction (PPI) for any one of the five SRIF G-protein coupled receptors (GPCRs). Since the detailed structure(s) of these membrane-embedded receptors is unknown (no X-ray structure!), the result described here may be useful for modeling structures by comparing the affinities of the numerous known somatostatin mimics.
authors.affiliation: Eidgenössische Technische Hochschule Zürich, Departement Chemie und Angewandte Biowissenschaften, Laboratorium für Organische Chemie, Wolfgang-Pauli-Strasse 10, Hönggerberg, HCI, CH-8093 Zürich.
authors.forename: James
authors.initials: J
authors.lastname: Gardiner
authors.forename: Daniel
authors.initials: D
authors.lastname: Langenegger
authors.forename: Daniel
authors.initials: D
authors.lastname: Hoyer
authors.forename: Albert K
authors.initials: AK
authors.lastname: Beck
authors.forename: Raveendra I
authors.initials: RI
authors.lastname: Mathad
authors.forename: Dieter
authors.initials: D
authors.lastname: Seebach
mesh_terms: D002942:Circular Dichroism; D006801:Humans; D019906:Nuclear Magnetic Resonance, Biomolecular; D015282:Octreotide / Q000031:analogs & derivatives* / Q000378:metabolism*; D010456:Peptides, Cyclic / Q000378:metabolism; D017481:Receptors, Somatostatin / Q000378:metabolism*; D013237:Stereoisomerism
chemical_list: D010456:Peptides, Cyclic; D017481:Receptors, Somatostatin; C470036:octreotate, Tyr(3)-; D015282:Octreotide