FAST-NMR

It is important to emphasize that the presence of two or three basic centres of comparable basicity in a conjugated molecule may lead to protonation processes at all of them. These processes may occur at various rates, but if all the rates are fast, nmr spectra do not enable us to say what are the relative amounts of variously protonated species present at equilibrium. Increasing the acidity of the medium and lowering the temperature in order to observe the resonances of the captured proton may have the effect of shifting the tautomeric equilibria in favour of one or other of the protonation sites. Information on the position of tautomeric equihbria in protonation processes is thus not obt iinable from nmr spectra under the conditions of rapid proton exchange. 

E. H. Hardy, A. Detken and B. H. Meier, Fast-NMR total through-bond correlation spectroscopy using adiabatic pulses. J. Magn. Reson., 2003, 165. 208-218. 

Mehdi M, Alan SS, Jeffrey CH (2006) Spectral Reconstmction Methods in Fast NMR Reduced Dimensionality, Random Sampling, and Maximum Entropy Reconstruction. J Magn Reson 192 96-105... 

A distinct feature of NMR spectroscopy, the possibility to simultaneously observe hundreds of atoms in complex macromolecules, finds its foundation in the invention of multidimensional experiments almost 40 years ago [1,2]. The approach, however, has an important caveat the ultimate resolution obtained in multidimensional experiments comes at a very high price, the long data collection times needed to systematically sample the large multidimensional spectral space. The number of measured data points increases polynomially with the spectrometer field and the desired spectral resolution, and exponentially with the number of dimensions. The problem of lengthy sampling compromises or even prohibits many applications of multidimensional spectroscopy in chemistry and molecular biology. Fortunately, the advent of fast NMR spectroscopy offers a number of solutions. 

Keywords Dmg discovery, FAST-NMR, In silica screening, Ligand affinity screens, Molecular docking. Nuclear magnetic resonance, Virtual screening... 

Powers R, Mercier KA, Copeland JC (2008) The application of FAST-NMR for the identification of novel drag discovery targets. Drag Discov Today 13(3 ) 172-179... 

Mercier KA et al (2006) FAST-NMR functional annotation screening technology using NMR spectroscopy. J Am Chem Soc 128(47) 15292-15299... 

Pintacuda G, Park AY, Keniry MA et al (2006) Lanthanide labeling offers fast NMR approach to 3D structure determinations of protein-protein complexes. J Am Chem Soc 128 3696-3702... 

The PRE may also be used for other than structural purposes. Theillet et proposed the use of PRE to improve sensitivity of fast NMR... 

R. Powers, K. A. Mercier and J. C. Copeland, The Application of FAST-NMR for the Identification of Novel Drug Discovery Targets , Drug Discov. Today, 2008, 13, 172. 

B.E. Coggins, R.A. Venters, P. Zhou, Radial samphng for fast NMR concepts and practices over three decades. Prog. Nucl. Magn. Reson. Spectrosc. 57 (4) (2010) 381-419. http //dx.doi.Org/10.1016/j.pnmrs.2010.07.001. 

The aim of this article is to compile all new HSQC-related NMR experiments published in the last years that have been specifically designed and applied to small molecules at natural abundance (Scheme 1). Special focus will be made on novel HSQC schemes including concepts such as fast NMR and pure shift NMR. In addition, reference to improved J-compensated HSQC sequences will be made, discussing the effects of the intensity and phase signal modulation dependence with respect to J(CH) and/or J(HH) which are generated during INEPT periods. A particular analysis will be also made on modem NMR methods designed for the quantitative measurement of J(CH) and/or D(CH) and, by... 

There has always been a general interest to develop fast NMR methods to reduce the experimental time required for a complete 2D acquisition and to economize valuable spectrometer time. There are two main factors that determine the overall duration of a given 2D experiment (i) the long recycle delay (typically in the order of some seconds) needed to achieve a preequilibrium proton polarization and (ii) the number of variable linearly sampled t increments required for an optimum resolution in the indirect FI dimension. Several approaches to accelerate data acquisition in HSQC experiments have been reported. 

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