Chenoweth, David M. and Harki, Daniel A. and Dervan, Peter B. (2009) Solution-phase synthesis of pyrrole-imidazole polyamides. Journal of the American Chemical Society, 131 (20). pp. 7175-7181. ISSN 0002-7863 http://resolver.caltech.edu/CaltechAUTHORS:20090723-113013566
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Pyrrole−imidazole polyamides are DNA-binding molecules that are programmable for a large repertoire of DNA sequences. Typical syntheses of this class of heterocyclic oligomers rely on solid-phase methods. Solid-phase methodologies offer rapid assembly on a micromole scale sufficient for biophysical characterizations and cell culture studies. In order to produce gram-scale quantities necessary for efficacy studies in animals, polyamides must be readily synthesized in solution. An 8-ring hairpin polyamide 1, which targets the DNA sequence 5′-WGWWCW-3′, was chosen for our synthesis studies as this oligomer exhibits androgen receptor antagonism in cell culture models of prostate cancer. A convergent solution-phase synthesis of 1 from a small set of commercially available building blocks is presented which highlights principles for preparing gram quantities of pyrrole−imidazole oligomers with minimal chromatography.
|Additional Information:||© 2009 American Chemical Society. Published In Issue: May 27, 2009; Article ASAP: May 04, 2009; Received: February 19, 2009. This work was supported by the National Institutes of Health (GM27681). DMC is grateful for a Caltech Kanel predoctoral fellowship. DAH thanks the California Tobacco-Related Disease Research Program (16FT-0055) for a postdoctoral fellowship. The National Science Foundation Chemistry Research Instrumentation and Facilities Program (CHE-0541745) is acknowledged for providing the UPLC-MS instrument. Supporting Information Available: 1H and 13C NMR spectra for synthesized compounds. This material is available free of charge via the Internet at http://pubs.acs.org.|
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|Deposited By:||Jason Perez|
|Deposited On:||10 Aug 2009 23:07|
|Last Modified:||26 Dec 2012 11:06|
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