X-ray crystallography and NMR

Pikromycin. Pikromycin (19, R = OH, R = H), the first macroHde discovered (77,78), is produced by S.felleus. Pikromycin is identical to amaromycin and albomycetin (79—81) and may be identical to proactinomycin (82—84). The stmcture of pikromycin was deterrnined from chemical degradation, mass spectrometry, nmr, and x-ray crystallography (85—90). Its aglycone, pikronoHde (20, R = OH), was produced by S. vene elae (36). A derivative, kromycin (22, R = OH), was formed from pikromycin under acidic conditions (87,88,91) and more drastic conditions produced an intramolecular spHoketal of pikronoHde named kromin (89,91). 10,11 -Oihydropikromycin (21, R = OH, R = H), was also produced by S. vene elae (92). 

Fig. 3.3 H NMR and X-ray crystallography study of the bis-ether complex 28. [Denmark, S.E. Edwards, ).P. Wilson, S.R.J. Am. Chem. Soc. 1992, 114, 2592. Reprinted with permission from The American Chemical Society]...

Structural Studies of Peptoids with Aliphatic Side Chains by CD, NMR, and X-ray Crystallography... 

Gooley PR, O Connell JF, Marcy AI, Cuca GC, Hagmann WK, Caldwell CG, Axel MG, Becker JW. Comparison of the structure of human recombinant short form stromelysin by multidimensional heteronuclear NMR and X-ray crystallography. J Biomol NMR 1996 7 8-28. 

Thus solid state NMR can be considered as a (potential) bridge between solution NMR and X-ray crystallography. 

Reaction of the 2-aminooxazoline 160 with the piperidinone 161 under basic conditions gives a mixture of linear and angular oxazolopyridopyrimidines, 162 and 163, the stmctures of which were confirmed by nuclear magnetic resonance (NMR) and X-ray crystallography of some derivatives (Equation 40) <1999T12819>. 

Structural proteomics aims the determination of three-dimensional protein structures in order to better understand the relationship between protein sequence, structure, and function. NMR and x-ray crystallography have been significant methods and indispensable tools to determine the structure of macromolecules, especially proteins. Many biotechnology companies have been using these two techniques for enlightening protein structure (Table 5.5). 

In this overview of fragment-based drug design, we will expand on the application of NMR and X-ray crystallography as the tools for biophysical screening. Common protocols will be presented, as well as the strengths and limitations of each approach. 

It is usual for NMR spectroscopy to be employed together with other physicochemical methods in a complementary manner. Combined use of NMR and X-ray crystallography is already a main stream among the methodologies of physical organic chemistry. It must be pointed out that not only the combination of solution NMR and X-ray analysis but also that of solid-state NMR and X-ray analysis is possible. 

The spirobenzoxazepine 28 was studied by 2-D and nuclear Overhauser enhancement Spectroscopy (NOESY) NMR and X-ray crystallography, and in both cases the same chair conformation, 28, was formed (See Figure 5). The authors conclude that this compound 28 is a semirigid scaffold, able to present various substituents without undergoing hydrophobic collapse, and 28 behaves structurally as a privileged structure <2004TL1051>. 

The structure of the N-terminal DCX domains has been solved to high resolution by NMR and X-ray crystallography (Fig. 7A). The domains have also been imaged bound to microtubules (Moores et aL, 2004), making doublecortin the only MAP, apart from tau and MAP2c (Al-Bassam et aL, 2002 Kar et aL, 2003a) to have been studied so far by 3D analysis of EM images. 

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