Bis-daunomycin hydrazones: interactions with DNA.
A series of bis-daunomycin hydrazones were synthesised from diester diamide linking groups derived from alpha,omega-dicarboxylic acids. All members of the series bis-intercalated into DNA, as evidenced by doubling of the lengthening of rod-like DNA compared to daunomycin, and by a 1000-5000 fold slower dissociation from DNA than daunomycin under detergent sequestration conditions. The bis-hydrazones exhibited neighbour exclusion, and occupied 6 bp under saturating conditions of drug. A unique DNA sequence specificity was apparent from transcriptional footprinting of 100 bp of DNA, with the greatest preference for 5'-CACA sites.
Phillips
D R
DR
Department of Biochemistry, La Trobe University, Bundoora, Victoria, Australia.
Brownlee
R T
RT
Reiss
J A
JA
Scourides
P A
PA
D000818:Animals; D001483:Base Sequence; D002417:Cattle; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D003630:Daunorubicin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D006835:Hydrazones / Q000138:chemical synthesis* / Q000494:pharmacology; D007364:Intercalating Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D008956:Models, Chemical; D014158:Transcription, Genetic / Q000187:drug effects
D006835:Hydrazones; D007364:Intercalating Agents; D004247:DNA; D003630:Daunorubicin