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Proceedings of the 31 st European Peptide SymposiumMichal Lebl, Morten Meldal, Knud J. Jensen, Thomas Hoeg-Jensen (Editors)European Peptide Society, 2010Chemical Modification of Natural ImmunomodulatorsTuftsin and Muramyl Dipeptide Significantly InfluenceTheir Biological ActivityAnna Wardowska 2 , Krystyna Dzierzbicka 1 , Małgorzata Rogalska 2 ,and Piotr Trzonkowski 21 Department of Organic Chemistry, Faculty of Chemistry, Technical University of Gdansk,Poland; 2 Laboratory of Clinical Immunology and Transplantology, Department ofImmunology, Medical University of Gdansk, PolandIntroductionTuftsin and muramyl dipeptide (MDP) are well known particles displaying variousimmunomodulatory properities [1]. In this study, we are continuing our program ofsyntheses of muramyl dipeptide (MDP) and nor-muramyl dipeptide (nor-MDP) conjugatesas potential immunomodulators [2-4]. We designed novel conjugates of MDP or nor-MDPwith tuftsin and retro-tuftsin derivatives containing isopeptide bond (Figure 1).Results and DiscussionThe aim of this study was to asses the influence of the synthesized compounds on theviability of white blood cells: either heterogenous population of peripheral bloodmononuclear cells (PBMC) or peripheral blood leukocytes (PBL) and isolated monocytes.The next step was to asses the observed influence on immune cells by determining thecytokine profile stimulated by the examined compounds. We analyzed three cytokines: twoproinflammatory (IL-6, TNF ), as well as anti-inflammatory (IL-10).Viability tests: PBMC – the viability of those cells was higher after incubation withthe following conjugates: 10, 11, 12 and 13; PBL – isolated leukocytes were most viable inpresence of the above mentioned compounds (10-13) as well as conjugates 2 and 6;monocytes – only conjugates 5, 12 and 14 had promising impact on the viability of thisphagocytes. The examined conjugates had little impact on TNF production by PBMC,only compounds 7 and 14 slightly induces the secretion of this cytokine. The otheranalysed proinflammatory cytokine – IL-6 – was secreted on higher levels in presence ofseveral conjugates: 2, 5 and 13, but the most active in this filed were 7 and 14. Examinedconjugates merely influenced anti-inflammatory cytokine production – IL-10.We assume that the analysis of the cytokine profile will confirm our assumption thatexamined conjugates of tuftsin and MDP are capable of activating antibacterialmechanisms by switching on Th1 immune response.358