In Vitro Selection of Peptides Targeting Human Telomerase RNA

Telomerase is an attractive anti-cancer target since it is expressed in most tumor cells but not in most normal cells. It is a ribonucleoprotein, composed of telomerase RNA and telomerase reverse transcriptase. We have targeted two functionally vital domains of telomerase RNA, P6.1 and CR7, using mRNA display. From peptide libraries of 10 or 100 trillion members, we have isolated Land D-peptides that bind with low nanomolar affinity and are highly specific for their cognate RNA target. These peptides are highly basic and are predicted to form -helicies, however non-electrostatic interactions contribute to overall peptide binding. Our data argue that very few random peptides bind RNA with high affinity and specificity. We expect that the peptides we have selected should bind in the context of telomerase RNA and will inhibit telomerase activity.