Rational drug design and high-throughput techniques for RNA targets.
RNA molecules are the only known molecules which possess the double property of being depository of genetic information, like DNA, and of displaying catalytic activities, like protein enzymes. RNA molecules intervene in all steps of gene expression and in many other biological activities. Like proteins, RNAs achieve those biological functions by adopting intricate three-dimensional folds and architectures. Further, as in protein sequences, RNA sequences contain signatures specific for three-dimensional motifs which participate in recognition and binding. In regulatory pathways, RNA molecules exist in equilibria between transient structures differentially stabilized by effectors such as proteins or cofactors. Therefore, RNA molecules display their potential as drug targets on different levels, namely in three-dimensional folds, in structural equilibria and in RNA-protein interfaces. Several examples will be described together with the already available techniques for combinatorial synthesis and high-throughput screening of potential drug and target RNA molecules.
Hermann
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Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. Thermann@sbnmr1.ski.mskcc.org
Westhof
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D001483:Base Sequence; D020650:Combinatorial Chemistry Techniques; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D012313:RNA / Q000737:chemistry / Q000187:drug effects*
D012313:RNA