Immunosuppressive activity of some peptides related to cycloamanide A (CyA A) and to the active fragment of a peptide immunomodulator from ovine colostrum.
A series of linear and cyclic hexapeptides, consisting of: Phe-Phe-Val-Pro-Gly-Ala, Tyr-Phe-Val-Pro-Gly-Ala, Phe-Tyr-Val-Pro-Gly-Ala, D-Phe-Tyr-Val-Pro-Gly-Ala, D-Tyr-Phe-Val-Pro-Gly-Ala, D-Tyr-Tyr-Val-Pro-Gly-Ala, c-(Phe-Tyr-Val-Pro-Gly-Ala-), c-(Tyr-Tyr-Val-Pro-Gly-Ala-) was synthesized and examined for the influence on humoral immune response by the plaque forming cell test. The peptides are related to Tyr-Val-Pro-Gly-Phe-Pro hexapeptide (an active fragment of immunomodulatory polypeptide found in sheep colostrum) and to the retro-sequence of cycloamanide A, a peptide immunosuppressor present in the mushroom Amanita phalloides. We found that substitution of one or both phenylalanine residues of the linear retro-sequence of cycloamanide A by tyrosine, enhances the immunosuppressive activity of the peptide. The inversion of configuration of N-terminal aromatic residues preserves the immunosuppressive activity. However, in this case, application of higher doses of the peptides decreases their activity. The highest immunosuppressive potency was found for Phe-Tyr-Val-Pro-Gly-Ala hexapeptide, which is most closely related to the active fragment of a peptide immunomodulator from the ovine colostrum, investigated by us previously.
Bolewska-Pedyczak
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Institute of Chemistry, Wrocław University, Poland.
Wieczorek
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Z
Zimecki
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Siemion
I Z
IZ
D000276:Adjuvants, Immunologic / Q000138:chemical synthesis* / Q000494:pharmacology*; D000595:Amino Acid Sequence; D000818:Animals; D003126:Colostrum / Q000737:chemistry / Q000276:immunology*; D005260:Female; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D051379:Mice; D008808:Mice, Inbred CBA; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000494:pharmacology*; D010446:Peptide Fragments / Q000138:chemical synthesis* / Q000494:pharmacology*; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000494:pharmacology*; D011247:Pregnancy; D011487:Protein Conformation; D012756:Sheep; D013329:Structure-Activity Relationship
D000276:Adjuvants, Immunologic; D007166:Immunosuppressive Agents; D009842:Oligopeptides; D010446:Peptide Fragments; D010456:Peptides, Cyclic; C036782:cycloamanide A