TUFTSIN-THF-GAMMA-2 CHIMERIC PEPTIDES - POTENTIAL NOVEL IMMUNOMODULATORS

Synthesis of two chimeric peptides composed of tuftsin and thymic humo ral factor-gamma 2 (THF-gamma 2) conjugates was accomplished. Our goal was the generation of novel immunomodulators. Initially, we demonstra te an IL-6 inducing activity of the phagocytic cells stimulant, tuftsi n, on murine macrophages. This activity was documented only in the pre sence of antigen, either KLH or lysozyme. The augmentation was dose de pendent, with optimal activity at a concentration of 200 and 20 nM, re spectively. The chimeric peptides, either H2N-tuftsin-THF-gamma 2-OH o r H2N-THF-gamma 2-tuftsin-OH, were also evaluated in the IL-6 system i n the presence of the more potent antigen, KLH. The IL-6 inducing effe ct was maintained, although maximal activity appeared only at a concen tration an order of magnitude greater than that of tuftsin. The chimer ic peptides were further tested in an assay evaluating enhancement in murine bone marrow myeloid colony formation, a system in which THF-gam ma 2, a T cell stimulant, has an established beneficial effect. The co mpounds were found to be inactive at the 25-200 ng/ml (14-112 nM) conc entration 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 eit her parent peptide, thus representing a possible therapeutic agent.