Synthesis and reactions with DNA of a family of DNA-DNA afinity cross-linking agents

Snorri Th Sigurdsson, Paul B. Hopkins

Research output: Contribution to journalArticlepeer-review

Abstract

A family of DNA-DNA cross-linking agents has been synthesized, in which 2,3-bis-(hydroxymethyl)-pyrrole is linked to the oligopeptide distamycin. These substances were efficient, sequence selective, DNA-DNA interstrand and intrastrand cross-linking agents. Substance 1a formed interstand and intrastrand cross-links at the sequences 5′ d(CGAATT) and 5′ d(GGAATT), respectively. The lesions from hydrolysis of the phosphodiester backbones of inter- and intrastrand cross-linked DNA were identical, and possessed the structure 20. Substance 1a was 1000-fold more active as a cross-linking agent than 2,3-bis-(hydroxymethyl)-1-methylpyrrole (19). The cytotoxicity of 2a was comparable to cis-DDP.

Original languageEnglish
Pages (from-to)12065-12084
Number of pages20
JournalTetrahedron
Volume50
Issue number42
DOIs
Publication statusPublished - 1994

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