Completion of a Programmable DNA-Binding 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 7-base-pair sequences of the general form 5'-WWGNNNW-3' (where W = A or T, N = W, G, or C). Their equilibrium association constants (K(a)) range from K(a) = 1×10(8) M(-1) to 4×10(10) 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
Carey F
CF
Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125.
Phillips
John W
JW
Trauger
John W
JW
Farkas
Michelle E
ME
Belitsky
Jason M
JM
Heckel
Alexander
A
Olenyuk
Bogdan Z
BZ
Puckett
James W
JW
Wang
Clay C C
CC
Dervan
Peter B
PB