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The Enantiomer of Octreotate Binds to All Five Somatostatin Receptors with Almost Equal Micromolar Affinity – A Comparison with SANDOSTATIN ®
Author(s) -
Gardiner James,
Langenegger Daniel,
Hoyer Daniel,
Beck Albert K.,
Mathad Raveendra I.,
Seebach Dieter
Publication year - 2008
Publication title -
chemistry and biodiversity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.427
H-Index - 70
eISSN - 1612-1880
pISSN - 1612-1872
DOI - 10.1002/cbdv.200890110
Subject(s) - somatostatin , somatostatin receptor , chemistry , receptor , enantiomer , affinities , octreotide , g protein coupled receptor , binding affinities , peptide , stereochemistry , somatostatin receptor 2 , biochemistry , endocrinology , biology
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 μ M , 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.