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.