Synthesis and biological studies on analogs of cyclolinopeptide A with a shortened peptide chain.
Continuing our work on the immunosuppressive activity of cyclolinopeptide A (CLA), a cyclic nonapeptide of the sequence: c-(-Leu-Ile-Ile-Leu-Val-Pro-Pro-Phe-Phe), we synthesized a series of 6 linear analogs of CLA, successively shortened at the N-terminus of the peptide chain. Immunosuppressive activity of acetates as well as trifluoroacetates of these peptides was investigated using PFC (humoral immunity) and DTH (cellular immunity) tests. It was found that the immunosuppressive potency of the peptides examined diminishes with shortening of the peptide chain. Octapeptide I with the sequence Ile-Ile-Leu-Val-Pro-Pro-Phe-Phe was found to be the most active of the whole series. The immunosuppressive activity increased again for a tripeptide fragment of CLA of the sequence Pro-Phe-Phe. The immunosuppressive activity of octapeptide probably depends on the suppression of IL-1, IL-6 and TNF production by the cells involved in immune and inflammatory response.
Siemion
I Z
IZ
Institute of Chemistry, Wrocław University, Poland.
Pedyczak
A
A
Strug
I
I
Wieczorek
Z
Z
D000595:Amino Acid Sequence; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007111:Immunity, Cellular / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D051379:Mice; D008808:Mice, Inbred CBA; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis* / Q000494:pharmacology*; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000494:pharmacology*; D012756:Sheep; D013329:Structure-Activity Relationship; D014269:Trifluoroacetic Acid
D007166:Immunosuppressive Agents; D010455:Peptides; D010456:Peptides, Cyclic; C055018:cyclolinopeptide A; D014269:Trifluoroacetic Acid