Chemical and Pharmaceutical Bulletin
Online ISSN : 1347-5223
Print ISSN : 0009-2363
Effect of Polymethylene and Phenylene Linking Groups on the DNA Cleavage Specificity of Distamycin-Linked Hydroxamic Acid-Vanadyl Complexes
Shigeki HASHIMOTOTakahiro INUIYushin NAKAMURA
Author information
JOURNALS FREE ACCESS

Volume 48 (2000) Issue 5 Pages 603-609

Details
Download PDF (1503K) Contact us
Abstract

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·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·VO(II) complexes.

Information related to the author
© The Pharmaceutical Society of Japan
Previous article Next article

Recently visited articles
feedback
Top