Inhibition of telomerase activity by a cell-penetrating peptide nucleic acid construct in human melanoma cells

We investigated the effect of two peptide nucleic acids (PNAs), which are c omplementary to the RNA component of human telomerase, on the catalytic act ivity of the enzyme. PNAs induced a dose-dependent reduction of telomerase activity in cell extracts from human melanoma cell lines and surgical speci mens. To down-regulate telomerase in intact cells, we generated a chimeric molecule synthesized by coupling the 13-mer PNA to the Antennapedia peptide . The PNA construct induced a dose- and time-dependent inhibition of telome rase activity. However, a 20-day exposure to the PNA construct only caused a slight increase in melanoma cell doubling time and failed to induce any t elomere shortening. (C) 2000 Federation of European Biochemical Societies.