Immunosuppressive activity of some peptides related to cycloamanide A (CyA A) and to the active fragment of a peptide immunomodulator from ovine colostrum

Abstract

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.