DNA structure control by polycationic species

Polyamine, cobalt aremines, and di-metallo transition metal chelates

Alison Rodger*, Karen J. Sanders, Michael J. Hannon, Isabelle Meistermann, Andrew Parkinson, Daniel S. Vidler, Ian S. Haworth

*Corresponding author for this work

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Many polycationic species bind to DNA and induce structural changes. The work reported here is the first phase of a program whose long-term aim is to create a class of simple and inexpensive sequence-selective compounds that will enable enhanced DNA structure control for a wide range of applications. Three classes of molecule have been included in this work: the polyamine spermine (charge: 4+) and spermidine (charge: 3+) (which are known to induce a wide range of DNA conformational changes but whose binding modes are still not well understood); cobalt (III) ammine transition metal complexes as potential polyamine mimics and [Fe(H2O)6]3+; and the first member of a new class of di-metallo tris-chelated cylinders of helical structure (charge 4+). Temperature-dependent absorption, circular dichroism, linear dichroism, gel electrophoresis, and molecular modeling data are presented. The cobalt ammines prove to be effective polyamine mimics, although their binding appears to be restricted to backbone and major groove. All the ligands stabilize the DNA, but the 4+ di-iron tris-chelate does so comparatively weakly and seems to have a preference for single-stranded DNA. All the molecules studied bend the DNA, with the di-iron tris-chelate having a particularly dramatic effect even at very low drug load. (C) 2000 Wiley-Liss, Inc.

Original languageEnglish
Pages (from-to)221-236
Number of pages16
JournalChirality
Volume12
Issue number4
DOIs
Publication statusPublished - 2000
Externally publishedYes

Keywords

  • Circular dichroism
  • Gel electrophoresis
  • Linear dichroism
  • Metallohelicates

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