RNA as a drug target: chemical, modelling, and evolutionary tools.
Dramatic technical progress in RNA synthesis and structure determination has allowed several difficulties inherent to the preparation, handling and structural analysis of RNA to be overcome, and this has led to a wealth of information about RNA structure and its relationship with biological function. It is now fully recognized that RNA molecules intervene at all stages of cell life, not only because of key sequence motifs but also because of intricate three-dimensional folds. This realization has promoted RNA to a potential therapeutic target. As in protein motifs recognizing nucleic acids, groups of the molecule interacting with RNA contribute to specific binding through defined hydrogen bonds and van der Waals docking, while other parts contribute to the driving force of binding via less specific electrostatic interactions accompanied by water and ion displacement.
Hermann
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Institut de Biologie Moléculaire et Cellulaire du CNRS, Strasbourg, France.
Westhof
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D000617:Aminoglycosides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D006678:HIV / Q000187:drug effects / Q000235:genetics*; D008958:Models, Molecular; D012313:RNA / Q000737:chemistry* / Q000187:drug effects* / Q000378:metabolism; D016337:RNA, Catalytic / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D012335:RNA, Ribosomal / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D012367:RNA, Viral / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects* / Q000235:genetics
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D016337:RNA, Catalytic; D012335:RNA, Ribosomal; D012367:RNA, Viral; D012313:RNA