Syntheses and biological activities of sandostatin analogs containing stereochemical changes in positions 6 or 8

• Published in: BIOPOLYM 2000-05, Vol.53 (6), p.497-505
• Main Authors: Rueter, Jaimie K., Mattern, Ralph-Heiko, Zhang, Li, Taylor, John, Morgan, Barry, Hoyer, Daniel, Goodman, Murray
• Format: Article
• Language: English
• Subjects: allo-threonine; Animals; Binding Sites; biological activity; Chemical modification; Conformations; hsst receptor; Humans; hydroxyvaline; Molecular structure; octreotide; Octreotide - analogs & derivatives; Octreotide - chemical synthesis; Octreotide - chemistry; Octreotide - metabolism; Polypeptides; Radioligand Assay; Receptors, Somatostatin - metabolism; sandostatin; somatostatin; Stereochemistry; Stereoisomerism; synthesis; Synthesis (chemical); Threonine; Valine
• ISSN: 0006-3525; 1097-0282
• DOI: 10.1002/(SICI)1097-0282(200005)53:6<497::AID-BIP6>3.0.CO;2-Y

In a continuation of our research efforts on the design and synthesis of novel peptidomimetic structures, we have synthesized a series of sandostatin amide analogs in which stereoisomers of threonine and β‐hydroxyvaline(β‐Hyv) are employed. The analogs D‐Phe1‐c[Cys2‐Phe3‐D‐Trp4‐Lys5‐Xaa6‐Cys7]‐Xbb8‐NH2 (Xaa = allo‐Thr, D‐allo‐Thr , D‐β‐Hyv, β‐Hyv, D‐Thr, and Xbb = Thr or Xaa = Thr and Xbb = allo‐Thr, D‐allo‐Thr , β‐Hyv, D‐Thr ) explore the effects on biological activity of stereochemical modifications and β‐methylation at positions 6 or 8. By these modifications, we examine the role of the two residues in binding to somatostatin receptors. We describe the synthesis and biological activity of these analogs. In combination with the results of the conformational analysis, this study provides new insights into the structural requirements for the binding affinity of somatostatin amide analogs to somatostatin receptors [Mattern et al., Conformational analyses of sandostatin analogs containing stereochemical changes in positions 6 or 8]. © 2000 John Wiley & Sons, Inc. Biopoly 53: 497–505, 2000