title: Completion of a Programmable DNA-Binding Small Molecule Library.
abstract: 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.
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125.
authors.forename: Carey F
authors.initials: CF
authors.lastname: Hsu
authors.forename: John W
authors.initials: JW
authors.lastname: Phillips
authors.forename: John W
authors.initials: JW
authors.lastname: Trauger
authors.forename: Michelle E
authors.initials: ME
authors.lastname: Farkas
authors.forename: Jason M
authors.initials: JM
authors.lastname: Belitsky
authors.forename: Alexander
authors.initials: A
authors.lastname: Heckel
authors.forename: Bogdan Z
authors.initials: BZ
authors.lastname: Olenyuk
authors.forename: James W
authors.initials: JW
authors.lastname: Puckett
authors.forename: Clay C C
authors.initials: CC
authors.lastname: Wang
authors.forename: Peter B
authors.initials: PB
authors.lastname: Dervan