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Ecteinascidin 743: a minor groove alkylator that bends DNA toward the major groove.

Abstract：

:The ecteinascidins (Ets), which are natural products derived from marine tunicates, exhibit potent antitumor activity. Of the numerous Ets isolated, Et 743 is presently being evaluated in phase II clinical trials. Et 743 binds in the minor groove of DNA and alkylates N2 of guanine. Although structurally similar to saframycin, which exhibits poor activity in cellular assays, Et 743 has shown good efficacy as an antitumor agent. In this study, DNA structural distortions induced by Et 743 were examined to provide insight into the molecular basis for the antitumor activity of Et 743. Electrophoretic mobility shifts of ligated oligomers containing site-directed adducts were used to examine the extent and direction of the Et 743-induced bend. Surprisingly, we find that Et 743 bends DNA toward the major groove, which is a unique feature among DNA-interactive agents that occupy the minor groove.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Zewail-Foote M,Hurley LH

doi

10.1021/jm990241l

keywords:

subject

Has Abstract

pub_date

1999-07-15 00:00:00

pages

2493-7

issue

14

eissn

0022-2623

issn

1520-4804

pii

jm990241l

journal_volume

42

pub_type

杂志文章

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