Solution-phase synthesis of pyrrole-imidazole polyamides
Abstract
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.Attached Files
Accepted Version - nihms-115452.pdf
Supplemental Material - ja901307m_si_001.pdf
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Additional details
- PMCID
- PMC2689157
- Eprint ID
- 14655
- Resolver ID
- CaltechAUTHORS:20090723-113013566
- NIH
- GM-27681
- Caltech
- California Tobacco-Related Disease Research Program
- 16FT-0055
- NSF
- CHE-0541745
- Created
-
2009-08-10Created from EPrint's datestamp field
- Updated
-
2021-11-08Created from EPrint's last_modified field