Completion of a programmable DNA-binding small molecule library

TETRAHEDRON

卷:63

Article

Hsu, Carey F. ; Phillips, John W. ; Trauger, John W. ; Farkas, Michelle E. ; Belitsky, Jason M. ; Heckel, Alexander ; Olenyuk, Bogdan Z. ; Puckett, James W. ; Wang, Clay C. C. ; Dervan, Peter B.

关键词: molecular recognition;    gene regulation;    polyamide;    small molecule-nucleic acid interaction;   

DOI  :  10.1016/j.tet.2007.03.041

来源: Elsevier

【 摘 要 】

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 K-a = 1 x 10(8) to 4 x 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. (c) 2007 Elsevier Ltd. All rights reserved.

【 授权许可】

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