Tuftsin-THF-gamma 2 chimeric peptides: potential novel immunomodulators.
Synthesis of two chimeric peptides composed of tuftsin and thymic humoral factor-gamma 2 (THF-gamma 2) conjugates was accomplished. Our goal was the generation of novel immunomodulators. Initially, we demonstrate an IL-6 inducing activity of the phagocytic cells stimulant, tuftsin, on murine macrophages. This activity was documented only in the presence of antigen, either KLH or lysozyme. The augmentation was dose dependent, with optimal activity at a concentration of 200 and 20 nM, respectively. The chimeric peptides, either H2N-tuftsin-THF-gamma 2-OH or H2N-THF-gamma 2-tuftsin-OH, were also evaluated in the IL-6 system in the presence of the more potent antigen, KLH. The IL-6 inducing effect was maintained, although maximal activity appeared only at a concentration an order of magnitude greater than that of tuftsin. The chimeric peptides were further tested in an assay evaluating enhancement in murine bone marrow myeloid colony formation, a system in which THF-gamma 2, a T cell stimulant, has an established beneficial effect. The compounds were found to be inactive at the 25-200 ng/ml (14-112 nM) concentration range evaluated. Finally, the chimeric peptides were tested in a combined macrophages-T cells assay, i.e. antigen presentation, in which H2N-tuftsin-THF-gamma 2-OH was found to be more active than either parent peptide, thus representing a possible therapeutic agent.
Granoth
R
R
Department of Organic Chemistry, Weizmann Institute of Science, Rehovot, Israel.
Vadai
E
E
Burstein
Y
Y
Fridkin
M
M
Tzehoval
E
E
D000276:Adjuvants, Immunologic / Q000138:chemical synthesis / Q000302:isolation & purification / Q000494:pharmacology*; D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000276:immunology; D005260:Female; D015850:Interleukin-6 / Q000096:biosynthesis / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D009842:Oligopeptides / Q000138:chemical synthesis / Q000302:isolation & purification / Q000494:pharmacology*; D011993:Recombinant Fusion Proteins / Q000138:chemical synthesis / Q000302:isolation & purification / Q000494:pharmacology*; D014405:Tuftsin / Q000138:chemical synthesis / Q000302:isolation & purification / Q000494:pharmacology*
D000276:Adjuvants, Immunologic; D015850:Interleukin-6; D009842:Oligopeptides; D011993:Recombinant Fusion Proteins; C064563:thymic humoral factor gamma 2; D014405:Tuftsin