The REDOR approach is powerful, versatile, and applicable to many systems, yet there is no set protocol and is best appreciated by way of example. REDOR measurements can be implemented to determine the strength of dipolar couplings, and hence precise distances, between heteronuclei and can also be used as a spectroscopic filter. Since its introduction in 1989, REDOR has been implemented to examine composition, structure, and dynamics in diverse biological macromolecular and whole-cell systems including enzyme-cofactor-inhibitor ternary complexes, protein-protein complexes, lipid-embedded membrane proteins, bacteria-antibiotic complexes, and intact leaves 2β 5. Rotational-Echo DOuble-Resonance (REDOR) NMR 1, in particular, has played an often unique role in elucidating drug modes of action and in driving the design of new therapeutic candidates 2β 4. Solid-state NMR has emerged as a powerful tool to examine biologically relevant drugbound complexes of systems that pose a challenge to analysis by conventional methods. Determining the bio-active bound conformations of drugs and mapping their interactions with their targets with high resolution are crucial to understanding the molecular and chemical basis for drug modes of action. While there are tremendous opportunities and active research in the areas of protein therapy, immunotherapy, and gene therapy, most current therapies employ small-molecule drugs to influence biological and biochemical phenomena in the host. Ehrlich, illustratively emphasizes the ultimate goal of identifying a highly selective therapeutic strategy to exert its action with no side effects or toxicity. ![]() The notion of βthe magic bullet,β popularized by Dr. Drug design and discovery efforts are enormously interdisciplinary endeavors, involving small and large molecules, biological targets, and the complexities of human physiology and drug pharmacology. The translation of discoveries at the bench into therapies to prevent and treat human disease and to improve overall health is a grand challenge and ultimate goal of many basic science research programs and of much larger laboratories and companies that ultimately develop drugs and bring them to the clinic.
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