Cyclolinopeptides and their analogs--a new family of peptide immunosuppressants affecting the calcineurin system.
The results of the investigation of immunosuppressive activity of cyclolinopeptide A (CLA--cyclic hydrophobic nonapeptide present in the linseeds) and its analogs are discussed. The results obtained for other natural cyclic peptides showing structural similarities with CLA (antamanide, cycloamanides, hymenistatin, hymenamides) are also reviewed. It results from these investigations that the molecular mechanism of the CLA action is the same as that of cyclosporin A and FK-506 compound, i.e. it consists in formation of the complex with cyclophilin and inhibition--in this form--of the phosphatase activity of calcineurin. The results also suggest that the immunosuppressive activity of these compounds resides in their--Pro-Xxx-Phe- fragment, where Xxx is a hydrophobic (e.g. Leu, Val) or aromatic amino acid residue.
Siemion
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IZ
Faculty of Chemistry, University of Wrocław, Poland.
Cebrat
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M
Wieczorek
Z
Z
D000595:Amino Acid Sequence; D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008969:Molecular Sequence Data; D010456:Peptides, Cyclic / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D010456:Peptides, Cyclic; C055018:cyclolinopeptide A