Journal
JOURNAL OF MEDICINAL CHEMISTRY
Volume 52, Issue 23, Pages 7380-7388Publisher
AMER CHEMICAL SOC
DOI: 10.1021/jm900256f
Keywords
-
Categories
Funding
- National Institutes of Health [GM051747]
Ask authors/readers for more resources
Pyrrole-imidazole (Py-Im) hairpin Polyamides are a class of small molecule DNA minor groove binding compounds that have been shown to modulate endogenous gene expression in cell culture. Gene regulation by polyamides requires efficient cellular uptake and nuclear localization properties for candidate compounds. To further optimize Py-Im polyamides for enhanced potency in cell culture, a focused library of polyamides possessing various modifications at the C-terminus was synthesized and tested. Comparison of polyamide biological activity in two cell lines revealed tolerance for structural modifications and agreement in activity trends between cell lines. The use of an oxime linkage between the polyamide and ail aromatic functionality on the C-terminus resulted in a similar to 20-fold increase in the potency of polyamides targeted to the androgen response element (ARE) in LNCaP cells by measuring AR-activated PSA expression.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available