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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.

SUBMITTER: Hsu CF

PROVIDER: S-EPMC2151752 | biostudies-literature | 2007 Jul

REPOSITORIES: biostudies-literature

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Completion of a Programmable DNA-Binding Small Molecule Library.

Hsu Carey F CF 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

Tetrahedron 20070701 27

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 ...[more]

PMID: 18596841

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