Purines crystal structure/studies

The discovery of these base pairs, which imply the double helical structure of DNA, stimulated a series of crystal structural studies not only of complexes of purines and pyrimidines, but of other complexes involving related molecules and their derivatives. Although we can formulate a large number of possible heterocombinations in matrix form, as shown below these complexes are reluctant to crystallize even when there is spectroscopic evidence of hetero-complex formation in solution. This is presumably because self-(homo)-association is energetically more favorable and only in rare cases were crystals of hetero complexes actually formed. Because of their three hydrogen bonds, G-C complexes form and crystallize more readily. There have been many attempts to crystallize the Watson-Crick A-U base pair, but none was successful and it only formed when the dinucleoside phosphate adenylyl-3,5,-uridine (ApU [536]) or higher oligomers were crystallized (see Part III, Chapter 20). 

Figure 14 Chemical structures of l,N -ethenoadenosine 5 -monophosphate (8-AMP ) and of uridine 5 -0-thiomonophosphate (UMPS ), as well as of the dianion of the acyclic nucleotide analogue 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA ). To facilitate comparisons between e-AMP and AMP the conventional atom numbering for adenines is adapted, a procedure which is common [171]. The purine-nucleotide e-AMP [11-13] and the pyrimidine-nucleotide UMPS [11,14] are shown in their dominating anti conformation. H-NMR shift measurements have shown [176] that in solution PMEA adopts an orientation which is similar to the anti conformation of AMP this conclusion is in accord with a crystal structure study [177] of the H2(PMEA) zwitterion.

The calculations indicate, in the first place, that in all azapurines studied the relative stabilities of the three tautomers decrease in the order N(9)H > N(7)H > N(8)H and this even in the case when the N(7)H tautomer is more stable than the N(9)H tautomer in the corresponding purine. The N(8)H tautomers always appear as fundamentally the least stable, about 20-30 kcal/mole less stable than the two other tautomers. Although the problem of the crystal structure of the purines and, in particular, of the occurrence in the crystal of the N(7)H or N(9)H tautomers will be discussed in a later section, it may be useful to note here that while the presence of the... 

Ttoo surveys on bond lengths are available, based on crystal structure data from purines and pyrimidines, and from nucleosides and nucleotides [61, 62]. The results of these studies are summarized in Thble 7.19. 

The determination of crystal structures for many platinum metal—nucleobase complexes has elucidated many of the binding features, although the foregoing discussion is evidence of the complexity of these mixtures in solution. The bases studied range from unsubstituted purines and pyrimidines to the nucleosides and nucleotides. One feature of this area is the general difficulty of obtaining suitable crystalline samples of the sugar... 

Case study theophylline anhydrate and monohydrate The type of structural information that can be obtained from the study of the x-ray diffraction of single crystals will be illustrated through an exposition of studies conducted on the anhydrate and hydrate phases of theophylline (3,7-dihydro-l,3-dimethyl-LH-purine-2,6-dione). The unit cell parameters defining the two phases are fisted in Table 7.2, while the structure of this compound and a suitable atomic numbering system is located in Fig. 7.3. 

In all of the above crystal studies, bond lengths and bond angles were found to be similar to those of the corresponding purines. As with all X-ray diffraction work, it can not be assumed that a structure found in an anhydrous crystal would necessarily recur in a hydrated one (which, unfortunately, cannot always be obtained), nor do crystal studies necessarily reflect the tautomeric equilibrium attained in aqueous solution. 

This enzyme is of considerable biological, medicinal and commercial interest. It plays a fundamental role in purine metabolism, it degrades anticancer drugs being targeted to specific cancers and its absence is associated with severe T-cell deficiency. Crystals of the enzyme on a conventional source diffractometer did not diffract beyond 4 A resolution, a resolution which is not adequate to study the structural interactions with various substrates and inhibitors. With intense synchrotron X-radiation at Daresbury, data could be collected to between 3.2 A and 2.8 A resolution the data to 3.2 A (table 10.3) were sufficient to solve the structure. This is another example of time-dependent radiation damage. Very fast data collection methods at the SRS involved collection of 100 reflections per second, where one crystal was used for four minutes of exposure time. The structure has been described in Ealick et al (1990) (figures 10.5 and 2.1). 

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