title: Novel short oligonucleotide conjugates as inhibitors of human telomerase.
abstract: A series of oligonucleotide conjugates were designed and synthesized as novel inhibitors of human telomerase. These compounds contain a relatively short (6-7-mer) oligonucleotide domain, with an N3'-->P5' phosphoramidate (np) or thio-phosphoramidate (nps) backbone, targeted to the template region of the RNA component of the enzyme and various pendant groups attached to either their 5'- or preferably to the 3'-termini. The most potent compounds in the series inhibited telomerase with low nM IC50 values in biochemical assays whereas the cognate oligonucleotides without the pendant groups were significantly less active having IC50 values 100-1000-fold higher.
authors.affiliation: Geron Corporation, Menlo Park, California 94025, USA. kpongracz@geron.com
authors.forename: Krisztina
authors.initials: K
authors.lastname: Pongracz
authors.forename: Shihong
authors.initials: S
authors.lastname: Li
authors.forename: Brittney-Shea
authors.initials: BS
authors.lastname: Herbert
authors.forename: Ronald
authors.initials: R
authors.lastname: Pruzan
authors.forename: Ellen
authors.initials: E
authors.lastname: Wunder
authors.forename: Allison
authors.initials: A
authors.lastname: Chin
authors.forename: Mieczyslaw
authors.initials: M
authors.lastname: Piatyszek
authors.forename: Jerry
authors.initials: J
authors.lastname: Shay
authors.forename: Sergei M
authors.initials: SM
authors.lastname: Gryaznov
mesh_terms: D000577:Amides; D001483:Base Sequence; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D005456:Fluorescent Dyes; D006801:Humans; D009838:Oligodeoxyribonucleotides / Q000138:chemical synthesis* / Q000494:pharmacology; D010756:Phosphoric Acids; D013329:Structure-Activity Relationship; D019098:Telomerase / Q000037:antagonists & inhibitors*
chemical_list: D000577:Amides; D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D009838:Oligodeoxyribonucleotides; D010756:Phosphoric Acids; C011067:phosphoramidic acid; D019098:Telomerase