Saturation transfer double difference

For a proof of concept, Meinecke et aV reinvestigated this interaction by STD spectroscopy on liposome, embedded a bPs integrin. Recently, a further example 

To a large extent, NMR is, complementary to other techniques. The ability to detect weak binders under quasi-natural conditions is a particular advantage, making it ideally suited for the fragment-based approach for developing lead structures. 

Diercks, M. Coles and H. Kessler, Curr. Opin. Chem. Biol, 2001, 5, 285. 

Stockman and C. Dalvit, Prog. NucL Magnetic Reson. Spectrosc., 2002, 41, 187. 

Heller and H. Kessler, Drug Discov. Today, 2003, 8, 803. 

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Shirzadi A, Simpson MJ, Xu Y, Simpson AJ (2008) Application of saturation transfer double difference NMR to elucidate the mechanistic interactions of pesticides with humic acids. Environ Sci Technol 42 1084—1090... 

STDD saturation transfer double difference spectroscopy... 

Pereira, A., Pfeifer, T.A., Grighatti, TA., and Andersen, R.J. (2009) Functional cell-based screening and saturation transfer double-difference NMR have identified haplosamate A as a cannabinoid receptor agorrist. ACS Chem. Biol., 4,139-144. 

The free energy of activation for the proton shift process in the interconversion between tautomeric forms 8 and 9 was measured by the Fors6n-Hoffman double resonance saturation transfer method and determined to be 16.2 kcal mof1 (Figure 7) <20040BC1227>. This value was an average over three different structures (R = Me, Et, Pr1). 

The experiment described above is termed selective population transfer (SPT), or more precisely in this case with proton spin inversion, selective population inversion, (SPI). It is important to note, however, that the complete inversion of spin populations is not a requirement for the SPT effect to manifest itself. Any unequal perturbation of the lines within a multiplet will suffice, so, for example, saturation of one proton line would also have altered the intensities of the carbon resonance. In heteronuclear polarisation (population) transfer experiments, it is the heterospin-coupled satellites of the parent proton resonance that must be subject to the perturbation to induce SPT. The effect is not restricted to heteronuclear systems and can appear in proton spectra when homonuclear-coupled multiplets are subject to unsymmetrical saturation. Fig. 4.20 illustrates the effect of selectively but unevenly saturating a double doublet and shows the resulting intensity distortions in the multiplet structure of its coupled partner, which are most apparent in a difference spectrum. Despite these distortions, the integrated intensity of the proton multiplet is unaffected by the presence of the SPT because of the equal positive and negative contributions (see Fig. 4.19d). Distortions of this sort have particular relevance to the NOE difference experiment described in Chapter 8. 

Double-resonance spectroscopy involves the use of two different sources of radiation. In the context of EPR, these usually are a microwave and a radiowave or (less common) a microwave and another microwave. The two combinations were originally called ENDOR (electron nuclear double resonance) and ELDOR (electron electron double resonance), but the development of many variations on this theme has led to a wide spectrum of derived techniques and associated acronyms, such as ESEEM (electron spin echo envelope modulation), which is a pulsed variant of ENDOR, or DEER (double electron electron spin resonance), which is a pulsed variant of ELDOR. The basic principle involves the saturation (partially or wholly) of an EPR absorption and the subsequent transfer of spin energy to a different absorption by means of the second radiation, leading to the detection of the difference signal. The requirement of saturability implies operation at close to liquid helium, or even lower, temperatures, which, combined with long experimentation times, produces a... 

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