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Risultati sfruttabili
The research activities performed by the partners under the present project have led to synthesis and subsequent chemical and biological profiling of a novel class of immunosuppressive compounds. The compounds are water-soluble cyclic hexa-peptides of very facile chemical synthesis. They were obtained through molecular modelling approaches. In vitro characterisation showed that these compounds inhibit major histocompatibility complex (MHC)-dependent T cell activation events (proliferation and cytokine production) but not MHC-independent T cell activation events induced by polyclonal mitogens (e.g. PHA, ConA, anti-CD3 + anti-CD28). They affect both CD4-positive as well as CD8-positive T cell compartments. They were shown to inhibit activation of both naive and antigen-experienced T cells. In in-vivo experiments in experimental allergic encephalomyelitis (EAE), an animal model of multiple sclerosis, selected compounds of this class were shown to reduce severity of clinical scores as well as to reduce or eliminate lethality in disease-affected animals.
A patent application covering this class of compounds has been filed on May 20, 2001. The size of the cyclic peptides of this class suggests the possibility to apply peptidomimetic approaches in order to obtain fully organic molecules mimicking their biological activities.
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