Discovery of ligands by a combination of computational and NMR-based screening: RNA as an example target.

摘要: NMR for screening of knowledge-based focused libraries compounds provides an efficient, cost-effective method to develop promising drug leads that target functionally important RNA structures. A library may be constructed from virtual (i.e., computational) commercial or proprietary databases available binding the three-dimensional structure a selected target. Alternatively, with properties deemed desirable, e.g., molecular moiety commonly found in drugs known bind RNA. The ideally should composed small water-soluble, nonpeptide, nonnucleotide organic compounds. Various simple, robust experiments are described enable experimental such structure. Some rapid mapping interaction site on verify targeted is hit rather than double helical region occurring tetraloop. Other elucidation ligand's moiety. Of course, any thus identified represent scaffolds suitable easy chemical modification enhance their pharmaceutical subsequent development.