Immunomodulatory properties of new conjugates of muramyl dipeptide and nor-muramyl dipeptide with retro-tuftsin (Arg-Pro-Lys-Thr-OMe)

Abstract

Six new conjugates of muramyl dipeptide and nor-muramyl dipeptide with retro-tuftsin were synthesised at Gdansk University of Technology. All compounds were investigated at Medical University of Gdansk. Their immunomodulatory properties were assessed using in vitro cultures of human subpopulations of white blood cells (peripheral blood mononuclear cells, peripheral blood lymphocytes, monocytes). We examined the viability of blood cells incubated with examined conjugates, as well as their ability to stimulate secretion of cytokines (TNFα—tumour necrosis factor α, IL6—interleukin 6) and cytotoxic activity of NK (Natural Killer) cells. Complementation in biological activity of muramyl dipeptide (MDP) and tuftsin in conjugates proved to be beneficial in the field of immunoadjuvanticity. Our investigations proved that new conjugates acquired features that native immunomodulators did not reveal separately. In examined compound, the part responsible for inducing cytotoxic activity of NK cells was the tuftsin part of the conjugates. MDP in conjugates was responsible for compound-induced synthesis of TNFα. The results of our study imply usefulness of the examine compounds (mainly A and B), as potential therapeutic agents.