Effect of polymethylene and phenylene linking groups on the DNA cleavage specificity of distamycin-linked hydroxamic acid-vanadyl complexes.
Two types of distamycin-linked hydroxamic acids (DHA), which contain various lengths of polymethylene chains (PM-DHA) and relatively rigid phenylene ones (Ph-DHA), have been synthesized for the first time. Their DNA cleavage specificities were investigated by an end-labeled fragment cleavage experiment in the presence of vanadyl ion and hydrogen peroxide. The DNA cleavage by the PM-DHA x VO(II) complexes was shown to be very dependent on the length of the chain and the AT sequences. The tetramethylene DHA (1b) complex exhibited highly specific cleavage patterns flanking the 8 and 10 AT sites. Interestingly, the Ph-DHA complexes selectively cleaved the 5' end-labeled strand at the AT sites, but did not cleave the 3' end-labeled strand. The vanadyl complexing moieties and the local sequence conformation of the AT tract are suggested to contribute significantly to the DNA recognition of the PM-DHA x VO(II) complexes.
Hashimoto
S
S
Department of Biological Science and Technology, Science University of Tokyo, Yamazaki, Noda, Japan.
Inui
T
T
Nakamura
Y
Y
D000818:Animals; D002417:Cattle; D004247:DNA / Q000032:analysis / Q000737:chemistry; D053938:DNA Fragmentation / Q000187:drug effects*; D004214:Distamycins / Q000737:chemistry* / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D006877:Hydroxamic Acids / Q000737:chemistry* / Q000494:pharmacology*; D010957:Plasmids / Q000737:chemistry / Q000187:drug effects; D011108:Polymers / Q000737:chemistry* / Q000494:pharmacology; D011758:Pyrroles / Q000737:chemistry* / Q000494:pharmacology; D014638:Vanadates / Q000737:chemistry* / Q000494:pharmacology*
D004214:Distamycins; D006877:Hydroxamic Acids; D011108:Polymers; D011758:Pyrroles; D014638:Vanadates; C030000:stallimycin; D004247:DNA