Incorporation of favorable pharmaceutical properties is a prominent design feature of many successfully developed drugs. NMR spectroscopy is an essential tool in this process since it can be used to determine the solution conformation as well as the intramolecular hydrogen bonding pattern. Solution structures can be determined using NOEs/ROEs, but increasingly residual dipolar couplings (RDC) are being used to determine the conformation of lead compounds in a variety of solvents. This talk will review the use of RDC solution conformations in the drug design of both small molecules and cyclic peptides and highlight using this technique when a protein bound conformation is not available or when significant SAR disconnects are observed.
