Peptide conformations - 49(1): Synthesis and structure-activity relationships of side chain modified peptides of cyclo(-d-Pro-Phe-Thr-Lys-Trp-Phe-)
| Autor: | Horst Kessler, Max Frimmer, Kornelia Ziegler, A. Haupt, Manfred Schudok |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
chemistry.chemical_classification
Steric effects Magnetic Resonance Spectroscopy Molecular Structure Protein Conformation Stereochemistry Phalloidin Biological Transport Active Cholic Acids Biological activity Peptide Cholic Acid In Vitro Techniques Retro-Inverso Peptide Biochemistry Peptide Fragments Cyclic peptide Structure-Activity Relationship chemistry.chemical_compound Liver chemistry Side chain Animals Somatostatin Conformational isomerism |
| Zdroj: | International Journal of Peptide and Protein Research. 32:183-193 |
| ISSN: | 0367-8377 |
| DOI: | 10.1111/j.1399-3011.1988.tb00933.x |
| Popis: | Cyclic hexapeptide analogues representing the modified retro sequence of the amino acid residues 7-11 of natural somatostatin are known to protect liver cells from phalloidin poisoning. To determine the influence of steric, lipophilic, and charge effects on (a) the conformation of the backbone and the aromatic side chains and (b) the biological response, the side chains of Phe2, Lys4, and Phe6 of cyclo(-D-Pro1-Phe2-Thr3-Lys(Z)4-Trp5-Phe6-), 1a, one of the most active peptides found so far, were modified by various residues. The discussion of conformationally relevant parameters proves that neither backbone conformations nor populations of aromatic side chain rotamers were altered by these substitutions. The potency of these derivatives in a cytoprotection assay varies by at most one order of magnitude (more or less active than the parent peptide 1a). A qualitative evaluation of lipophilic, steric, and charge effects reveals the dominance of lipophilic effects of aromatic residues; the most potent compounds contain aromatic substructures in the side chain of Lys4. |
| Databáze: | OpenAIRE |
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