A backbone-cyclic, receptor 5-selective somatostatin analogue: synthesis, bioactivity, and nuclear magnetic resonance conformational analysis
| Autor: | Vered Hornik, Asher Gamliel, Chaim Gilon, Dvira Shohat, Gary Gellerman, Etty Feller, Oded Arad, Oved Amitay, Ofer Ziv, Barbara Mathä, Mazal Wanger, Horst Kessler, Martin Huenges, Michel M. Afargan |
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| Rok vydání: | 1998 |
| Předmět: |
Male
Magnetic Resonance Spectroscopy Stereochemistry Protein Conformation Enzyme-Linked Immunosorbent Assay CHO Cells Kidney Chemical synthesis Peptides Cyclic chemistry.chemical_compound Blood serum Cricetinae Drug Discovery Peptide synthesis Animals Humans Receptors Somatostatin Rats Wistar Receptor Pancreas chemistry.chemical_classification Chemistry Biological activity Blood Proteins Lipase Ligand (biochemistry) Glucagon Cyclic peptide Rats Somatostatin Growth Hormone Pituitary Gland Amylases Molecular Medicine Bombesin Ceruletide |
| Zdroj: | Journal of medicinal chemistry. 41(6) |
| ISSN: | 0022-2623 |
| Popis: | Cyclo(PheN2-Tyr-D-Trp-Lys-Val-PheC3)-Thr-NH2 (PTR 3046), a backbone-cyclic somatostatin analogue, was synthesized by solid-phase methodology. The binding characteristics of PTR 3046 to the different somatostatin receptors, expressed in CHO cells, indicate high selectivity to the SSTR5 receptor. PTR 3046 is highly stable against enzymatic degradation as determined in vitro by incubation with rat renal homogenate and human serum. The biological activity of PTR 3046 in vivo was determined in rats. PTR 3046 inhibits bombesin- and caerulein-induced amylase and lipase release from the pancreas without inhibiting growth hormone or glucagon release. The major conformation of PTR 3046 in CD3OH, as determined by NMR, is defined by a type II' beta-turn at D-Trp-Lys and a cis amide bond at Val-PheC3. |
| Databáze: | OpenAIRE |
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