SAR by 1D NMR.

1D NMR spectroscopy is a standard technique in the characterization of organic molecules. 1D NMR data inherently provide information on the conformational preferences of molecules, but this information is typically overlooked beyond the determination of compound identity and purity. Balazs and co-workers describe the use of routine 1D NMR spectra (chemical shifts, chemical shift dispersion, coupling constants) of molecules free in solution, in combination with protein target binding data, in order to identify conformational signatures of molecules when bound to their targets. Via case studies, they demonstrate the application of these conformational signatures observed in simple 1D NMR spectra in the optimization of compounds for medicinal chemistry, with particular application to the development of optimized linkers in the synthesis of macrocycles.