Synthesis of novel, highly potent cyclic-hexapeptide analogs of somatostatin. Potential application of orthogonal protection for affinity chromatography

✍ Scribed by Rolando A. Spanevello; Ralph Hirschmann; Karen Raynor; Terry Reisine; Ruth F. Nutt

• Book ID: 104225228
• Publisher: Elsevier Science
• Year: 1991
• Tongue: French
• Weight: 265 KB
• Volume: 32
• Category: Article
• ISSN: 0040-4039
• DOI: 10.1016/s0040-4039(00)92279-2

✦ Synopsis

The syntheses of new cyclic hexapeptides am described. These peptides potently displace [125a CGP-23996 (des-Alat, Glyz-d,samino-Cys~1Tyrt1]-dicarba %I4 SRIF) from SRlP receptors on AtT-20 cells. Two of these compounds are of potential value for the isolation of SRlF receptors by affiity chromatography.

A key feature in the design was the use of orthogonal protection to provide selective covalent bonding to the solid support. Somatostatin (SRIF) 1, a cyclic tetradecapeptide, was first isolated from bovine hypothalamus1 and characterized as an inhibitor of growth hormone secretion. SRIF receptors have been found not only on pituitary cells but also in the brain, on gastric and pancreatic cells, and elsewhere2 This has stimulated interest in the isolation of SRIF receptors by affinity chromatography in amounts sufficient for partial sequence determination. D-Trp* SRIF has been used successfully as an affinity ligand.3 We wished to design and synthesize smaller ligands which would be stable to proteolytic enzymes. We also sought a strategy which would permit attachment of the l&and to affinity gels at one selected position of the peptide. It has been qorted4~ that cyclic