Inhibition of vertebrate telomerases by the triphosphate derivatives of carbocyclic oxetanocin analogs.
Telomerase is a cellular endogenous reverse transcriptase that uses its internal RNA as a template for extension of the telomere repeat, thus maintaining telomere length. In order to clarify the susceptibility of telomerase to triphosphate derivatives of carbocyclic oxetanocins, inhibition by 9-[trans-trans-2,3-bis(hydroxymethyl)cyclobutyl]guanine triphosphate (C.OXT-GTP) and its methylene analog, 9-(cis-3-hydroxymethyl-2-methylenecyclobutyl)guanine triphosphate (m-C.OXT-GTP) was investigated. Both compounds showed potent inhibitory activity. Lineweaver-Burk plot analyses showed that the inhibition mode of these compounds was competitive with dGTP, the Ki values for C.OXT-GTP and m-C.OXT-GTP being 2.0 microM and 4.9 microM, respectively, and thus smaller than the Km of dGTP (11 microM).
D000225:Adenine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D006367:HeLa Cells; D006801:Humans; D012474:Salmon; D019098:Telomerase / Q000037:antagonists & inhibitors*
C051061:oxetanocin; D019098:Telomerase; D000225:Adenine