Replacement of the Bizelesin ureadiyl linkage by a guanidinium moiety retards translocation from monoalkylation to cross-linking sites on DNA

Seung Joo Lee, Frederick C. Seaman, Daekyu Sun, Heping Xiong, Robert C. Kelly, Laurence H. Hurley

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

In this contribution we demonstrate that Bizelesin can translocate along the minor groove of DNA from a kinetically favored monoalkylation site to a thermodynamically favored cross-linking site. This translocation is prevented in compounds that have a charged guanidino linkage substituting for the ureadiyl linkage. Furthermore, the manipulative interplay of Bizelesin and the target sequence 5'-TAATTA (Seaman, F.C.; Chu, J.; Hurley, L.H. J. Am. Chem. Soc. 1996, 118, 5383-5395) that is required to produce a suitably rearranged product for cross-linking is prevented by the substitution of a guanidino for the ureadiyl linkage. A structural basis involving hydrogen bonding of the guanidino linkage with phosphates on the backbone of DNA is proposed to account for the absence of translocation, the slow conversion of monoalkylated to cross-linked species, and the non-rearranged cross-linked product.

Original languageEnglish (US)
Pages (from-to)3434-3442
Number of pages9
JournalJournal of the American Chemical Society
Volume119
Issue number15
DOIs
StatePublished - Jun 11 1997
Externally publishedYes

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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