Issue 9, 2009

A new synthesis of alkene-containing minor-groove binders and essential hydrogen bonding in binding to DNA and in antibacterial activity

Abstract

A practical synthesis of alkene-containing minor-groove binders for DNA, related to distamycin, with potential for wide structural diversity is described, based upon the Wittig chemistry of N-alkylpyrrole aldehydes. The compounds prepared have been evaluated for binding to DNA by physical methods (melting temperature and NMR) and for their antibacterial activity. Significantly, it was found that alkenes linking the aryl head group of the minor-groove binder promote strong binding to DNA and high antibacterial activity against Gram-positive bacteria. Conversely, a minor-groove binder containing an alkene located towards the alkylamino tail group has a low affinity for DNA and does not show antibacterial activity. These observations suggest an important role for specific hydrogen bonds in the binding of compounds of this type to DNA, and in their antibacterial activity.

Graphical abstract: A new synthesis of alkene-containing minor-groove binders and essential hydrogen bonding in binding to DNA and in antibacterial activity

Supplementary files

Article information

Article type
Paper
Submitted
29 Jan 2009
Accepted
16 Feb 2009
First published
12 Mar 2009

Org. Biomol. Chem., 2009,7, 1843-1850

A new synthesis of alkene-containing minor-groove binders and essential hydrogen bonding in binding to DNA and in antibacterial activity

N. G. Anthony, D. Breen, G. Donoghue, A. I. Khalaf, S. P. Mackay, J. A. Parkinson and C. J. Suckling, Org. Biomol. Chem., 2009, 7, 1843 DOI: 10.1039/B901898K

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