Completion of a Programmable DNABinding Small Molecule Library
Hairpin pyrrole-imidazole (Py-Im) polyamides are programmable oligomers that bind the DNA minor groove in a sequence-specific manner with affinities comparable to those of natural DNA-binding proteins. These cell-permeable small molecules have been shown to enter the nuclei of live cells and downregulate endogenous gene expression. We complete here a library of 27 hairpin Py-Im polyamides, which bind seven-base-pair sequences of the general form 5′-WWGNNNW-3′ (where W=A or T, N=W, G, or C). Their equilibrium association constants (Ka) range from Ka=1×108 to 4×1010 M−1 with good sequence specificity. A table of binding affinities and sequence contexts for this completed 27-member library has been assembled for the benefit of the chemical biology community interested in molecular control of transcription.
Hsu, C. F., J. W. Phillips, J. W. Trauger, M. E. Farkas, et al. 2007. "Completion of a Programmable DNABinding Small Molecule Library." Tetrahedron 63(27): 6146-6151.
Chemistry and Biochemistry
Tetrahedron 50th Anniversary Symposium-in-Print (Part 2)