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Telomerase, the ends of linear Eukaryotic chromosomes, are critical for maintaining the stability of the genome. Telomeres are progressively shortened during each cycle of cell division. Upon reaching a critical length, programmed cell death (apoptosis) occurs. Ribonucleoprotein Telomerase acts to maintain or lengthen the Telomeres but is not active in normal somatic cells. Telomerase activity has been detected in most tumor cell lines and may be responsible for their immortalization, and increased Telomerase activity in rumors can be correlated to poorer clinical prognoses. Thus this enzyme is an attractive target for anticancer chemotherapies.

Two approaches are being examined for selective inhibition of Telomerase. The first involves targeting of the RNA-containing portion of the enzyme. This RNA serves as the template for extension of the telomeric repeat sequence. Modified nucleic acids such as 2’-O-methyl RNAs and peptide nucleic acids have been shown to bind to telomeric RNA in immortal human cells and inhibit Telomerase activity. This treatment ultimately resulted in cell death. These nucleic acid derivatives were chosen because of their resistance to nuclease degradation and high affinities for forming double-helical complexes with RNA. A second approach toward Telomerase inhibition involves use of medicine that bind to G-quadruplex DNA. Large aromatic molecules such as porphyrins and anthraquinones selectively bind and stabilize G- quadruplex DNA structures. Although in vivo existence of G-quadruplex has not been demonstrated, some of these compounds have been shown to inhibit Telomerase activity. Further studies will be necessary to determine antitumor activities of these compounds.