DNA-BINDING PYRROLE AND IMIDAZOLE POLYAMIDE DERIVATIVES

摘要

Novel small molecule polyamides of Formula (I) that specifically bind withsubnanomolar affinity to any predetermined sequence in the human genome withpotential use in molecular biology and human medicine are described. Further,the designed compounds which target the minor groove of B-form double helicalDNA offer a general approach for the control of gene-expression. Simple rulesare disclosed which provide for rational control of the DNA-binding sequencespecificity of synthetic polyamides containing N-methylpyrrole and N-methylimidazole amino acids. A series of molecular templates for polyamidedesign are disclosed which provide for small molecules which recognizepredetermined DNA sequences with affinities and specificities comparable tosequence specific DNA-binding proteins such as transcription factors.