SYNTHESIS AND CHARACTERIZATION OF A SPECIFIC PEPTIDE NUCLEIC-ACID THAT INHIBITS EXPRESSION OF INDUCIBLE NO SYNTHASE

Inducible nitric oxide synthase (iNOS) is modulated at the transcripti onal level. Overexpression of this protein may result in high levels o f nitric oxide leading to tissue damage and immunosuppression, In orde r to reduce the pathological effects of NO overproduction many efforts have been devoted to the identification of specific inhibitors of iNO S, The discovery of peptide nucleic acids (PNA), a novel class of mole cules able to selectively interact with nucleic acids, prompted us to attempt a new way for the regulation of NO production. Here we describ e the synthesis, characterization and in vitro effects of a PNA molecu le bearing a homopyrimidine sequence complementary to the 5' coding re gion of murine iNOS mRNA, This PNA shows specific interactions with iN OS mRNA in RNase protection assays and is able to block the synthesis of iNOS protein selectively in a rabbit reticulocyte lysate system. Th ese results strengthen the view of a possible pharmacological applicat ion of PNA as a compound able to interfere with a specific enzymatic a ctivity even at low concentrations. (C) 1998 Federation of European Bi ochemical Societies.