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Allosteric modulation of DNA by small molecules

Chenoweth, David M ; Dervan, Peter B

Proceedings of the National Academy of Sciences - PNAS, 2009-08, Vol.106 (32), p.13175-13179 [Periódico revisado por pares]

United States: National Academy of Sciences

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Título:
Allosteric modulation of DNA by small molecules
Autor: Chenoweth, David M ; Dervan, Peter B
Assuntos: Allosteric Regulation - drug effects ; Amino Acid Substitution ; Base Sequence ; Binding sites ; Cancer ; Crystal structure ; Crystallography, X-Ray ; Cyclization ; Deoxyribonucleic acid ; Disease ; DNA ; DNA - chemistry ; DNA - drug effects ; DNA - genetics ; DNA - metabolism ; Gene expression ; Genes ; Humans ; Hydrogen bonds ; Imidazoles ; Metastasis ; Models, Molecular ; Molecules ; Nucleic Acid Conformation - drug effects ; Nucleosomes ; Nylons - chemistry ; Nylons - metabolism ; Nylons - pharmacology ; Oligonucleotides ; Oxygen ; Physical Sciences ; Water - chemistry
É parte de: Proceedings of the National Academy of Sciences - PNAS, 2009-08, Vol.106 (32), p.13175-13179
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Author contributions: D.M.C. performed research; D.M.C. and P.B.D. analyzed the data; and D.M.C. and P.B.D. wrote the paper.
Contributed by Peter B. Dervan, June 17, 2009
Descrição: 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 helix 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.
Editor: United States: National Academy of Sciences
Idioma: Inglês

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Allosteric modulation of DNA by small molecules

Chenoweth, David M ; Dervan, Peter B

United States: National Academy of Sciences

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