Deoxyadenosine, structure

Koole LH, Buck HM, Nyilas A, Chattopadhyaya J (1987) Structural properties of modified deoxyadenosine structures in solution. Impact of the gauche and anomeric effects on the furanose conformation. Can J Chem 65 2089-2094... 

Modified Deoxyadenosine Structures in Solution. Impact of the Gauche and Anomeric Effects on the Furanose Conformation, Can. J. Chem. 65 2089 (1987). 

The numbering scheme used for nucleosides maintains the independence of the two structural units The pyrimidine or purine is numbered m the usual way So is the car bohydrate except that a prime symbol ( ) follows each locant Thus adenosine is a nude oside of D nbose and 2 deoxyadenosine is a nucleoside of 2 deoxy d ribose... 

The nucleoside cordycepin was isolated from cultures of Corofy- ceps militaris and found to be 3 deoxyadenosine Write its structural formula j... 

Very interesting information relevant to the stereochemical results of alkylation of DNA comes from studies of nucleosides alkylated by activated PAHs. Eight such structures have been reported (115-118). Three are products of the interaction of chloromethyl PAHs with N6 of adenosine XXX-XXXII, two with deoxyadenosine (XXXIII, XXXIV), two are para-substituted benzyl derivatives of guanosine, alkylated at 0-6 (XXXV, XXXVI) (117) and one is an acetyl aminofluorene derivative of guanosine, alkylated at C8 (XXXVII) (118). 

The general scheme for preparation of the alkylated adenosine and deoxyadenosine involved the interaction of the appropriate amino-hydrocarbon with a 6-chloropurine riboside (116). This allowed for the most specific interaction without too many byproducts. The molecular structures determined from diffraction studies are shown in Figures 24 and 25. In Figure 24 the shape of an alkylated nucleoside (115) is compared with that of the unalkylated form,... 

Figure 24. Comparison of the structures of (a) deoxyadenosine and (b) an alkylated derivative. Note the syn conformation of the product of alkylation.

It can be seen that alkylation has changed the sugar-base conformation (distant from the site of alkylation) from anti (as in deoxyadenosine and in B-DNA) to syn (as in alkylated deoxyadenosine and in some bases in Z-DNA). The sugar puckers are either C2 -endo or C3 -endo. A second structural feature of great interest in these crystals is that the more planar anthracene portion of the PAH is stacked between adenine residues of other molecules throughout the crystal. The highly buckled region of the PAH does not take part... 

Figure 4.12 The structures of the four bases (A, G, T and C) found in DNA and of a nucleoside (deoxyadenosine) and a nucleotide (deoxyadenosine-5 -triphosphate).

Figure 15.8 (a) Structure and (b) alternative conformations of cobalamine found in B12-dependent enzymes. The functional group R is deoxyadenosine in AdoCbl, methyl in MeCbl and -CN in vitamin B12. (From Bannerjee and Ragsdale, 2003. Reprinted with permission from Annual Reviews.)... 

In nature, eight common nucleotides exist, four found in DNA and four in RNA. In the standard abbreviations for DNA nucleotides, a lowercase d specifies the presence of deoxyribose. RNA nucleotides lack this designation. Nucleosides have names of one word (e.g., deoxyadenosine, cytidine, and uridine). The ending monophosphate completes the nucleotide names. Table 16.1 lists correct names for all common nucleotides and nucleosides, and Figure 16.9 shows linkages and structures for all eight nucleotides. 

So far only a few dozen organofluorine compounds have been isolated from living organisms, for example fluoroacetic acid, 4-fluorothreonine and rw-fluoro-oleic acid [244-246], The reason that nature has not invested in fluorine chemistry could be a combination of low availability of water-dissolved fluoride in the environment due to its tendency to form insoluble fluoride salts, and the low reactivity of water-solvated fluoride ion. However, in 2002, O Hagan and collaborators [247] published the discovery of a biochemical fluorination reaction in a bacterial protein extract from Streptomyces cattleya converting S-adenosyl-L-methionine (SAM) to 5 -fluoro-5 deoxyadenosine (5 -FDA). The same protein extract contained also the necessary enzymatic activity to convert 5 -FDA into fluoroacetic acid. In 2004, the same authors published the crystal structure of the enzyme and demonstrated a nucleophilic mechanism of fluorination [248,249]. 

Fig. 5. The X-ray-derived structure of the 5 -chloro-5 -deoxyadenosine (5 -CIDA)-fluorinase co-complex overlayed with the 5 -FDA structure. It can be seen that the chlorine atom is displaced relative to the location of the fluorine due to its larger size [15]. (See Colour Plate Section at the end of this book.)...

The adenine radical cation was observed in a single crystal of adenine hydrochloride hemihydrate [43]. In this crystal, the adenine is protonated at Nl. After electron loss, the molecule deprotonates at Nl, giving Ade(Nl -l-H, Nl-H). This produces a radical that is structurally equivalent to the cation of the neutral adenine molecule with spin density on C8 and N6 [p(C8) = 0.17 and p(N6) = 0.25]. The adenine radical cation is strongly acidic (pi a< 1) [22]. This strong driving force makes the reaction independent of environmental conditions. In single crystals of adenosine [42] and anhydrous deoxyadenosine [44], the N6 deprotonated cation [Ade(N6-H) ] is observed which is characterized by p(C8) = 0.16 and p(N6) = 0.42. The experimental isotropic hyperfine couplings are N6-H = 33.9 MHz and C8-H = 12.4 MHz. 

The purine ring-numbering scheme, 1, and structures of some simple purines, viz. adenine 2, guanine 3, caffeine 4, theophylline 5, adenosine 6, 2 -deoxyadenosine 7, guanosine 8, 2 -deoxyguanosine 9, xanthine 10, and hypoxanthine 11, are shown. 

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