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 Hurley

Research output: Contribution to journalArticle

12 Citations (Scopus)

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 - 1997
Externally publishedYes

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Guanidine
DNA
Hydrogen Bonding
Hydrogen bonds
Phosphates
Substitution reactions
bizelesin

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Replacement of the Bizelesin ureadiyl linkage by a guanidinium moiety retards translocation from monoalkylation to cross-linking sites on DNA. / Lee, Seung Joo; Seaman, Frederick C.; Sun, Daekyu; Xiong, Heping; Kelly, Robert C.; Hurley, Laurence.

In: Journal of the American Chemical Society, Vol. 119, No. 15, 1997, p. 3434-3442.

Research output: Contribution to journalArticle

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AU - Kelly, Robert C.

AU - Hurley, Laurence

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AB - 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.

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