Designed sequence-specific minor groove ligands.
In the past decade, a general design for sequence-specific minor groove ligands has evolved, based on the natural products distamycin and netropsin. By utilizing a basic set of design rules for connecting pyrrole, imidazole, and hydroxypyrrole modules, new ligands can be prepared to target almost any sequence of interest with both high affinity and specificity. In this review we present the design rules with a brief history of how they evolved. The structural basis for sequence-specific recognition is explained, together with developments that allow linking of recognition modules that enable targeting of long DNA sequences. Examples of the affinity and specificity that can be achieved with a number of variations on the basic design are given. Recently these molecules have been used to compete with proteins both in vitro and in vivo, and a brief description of the experimental results are given.
Department of Chemistry, University of California, Berkeley, USA. DEWemmer@LBL.gov
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D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D004247:DNA / Q000737:chemistry* / Q000235:genetics*; D004214:Distamycins / Q000494:pharmacology; D015195:Drug Design; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009429:Netropsin / Q000494:pharmacology; D009690:Nucleic Acid Conformation
D000998:Antiviral Agents; D004214:Distamycins; D008024:Ligands; D009429:Netropsin; C030000:stallimycin; D004247:DNA