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- W2158952548 abstract "Many human diseases are caused by dysregulated gene expression. The oversupply of transcription factors may be required for the growth and metastatic behavior of human cancers. Cell permeable small molecules that can be programmed to disrupt transcription factor-DNA interfaces could silence aberrant gene expression pathways. Pyrrole-imidazole polyamides are DNA minor-groove binding molecules that are programmable for a large repertoire of DNA motifs. A high resolution X-ray crystal structure of an 8-ring cyclic Py/Im polyamide bound to the central 6 bp of the sequence d(5′-CCAGGCCTGG-3′)2 reveals a 4 Å widening of the minor groove and compression of the major groove along with a >18 ° bend in the heli x axis toward the major groove. This allosteric perturbation of the DNA helix provides a molecular basis for disruption of transcription factor-DNA interfaces by small molecules, a minimum step in chemical control of gene networks." @default.
- W2158952548 created "2016-06-24" @default.
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- W2158952548 date "2009-08-11" @default.
- W2158952548 modified "2023-09-26" @default.
- W2158952548 title "Allosteric modulation of DNA by small molecules" @default.
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- W2158952548 doi "https://doi.org/10.1073/pnas.0906532106" @default.
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