Deoxyinosine

Adenosine deaminase (ADA) is an amino hydrolase that catalyzes the deamination of adenosine and 2 -deoxyadenosine to inosine and 2 -deoxyinosine, respectively. High activity of ADA is seen in thymus and other lymphoid tissues. ADA has been shown in many different physical forms. A small form of the enzyme predominates in the spleen, stomach, and red blood cells, whereas the large form predominates in the kidney, liver, and skin fibroblasts. The small form of the catalytic subunit can be converted to the large form by complexing with a protein termed binding protein or complexing protein. 

One-electron oxidation of the adenine moiety of DNA and 2 -deoxyadenos-ine (dAdo) (45) gives rise to related purine radical cations 46 that may undergo either hydration to generate 8-hydroxy-7,8-dihydroadenyl radicals (47) or deprotonation to give rise to the 6-aminyl radicals 50. The formation of 8-oxo-7,8-dihydro-2 -deoxyadenosine (8-oxodAdo) (48) and 4,6-diamino-5-formamidopyrimidine (FapyAde) (49) is likely explained in terms of oxidation and reduction of 8-hydroxy-7,8-dihydroadenyl precursor radicals 47, respectively [90]. Another modified nucleoside that was found to be generated upon type I mediated one-electron oxidation of 45 by photoexcited riboflavin and menadione is 2 -deoxyinosine (51) [29]. The latter nucleoside is likely to arise from deamination of 6-aminyl radicals (50). Overall, the yield of formation of 8-oxodAdo 48 and FapyAde 49 upon one-electron oxidation of DNA is about 10-fold-lower than that of 8-oxodGuo 44 and FapyGua 43, similar to OH radical mediated reactions [91]. 

Adenosine deaminase catalyzes the hydrolytic deamination of adenosine and 2 -deoxyadenosine to inosine and 2 -deoxyinosine respectively. Inhibition of adenosine deaminase leads to an accumulation of its substrates which results in adenosine receptor-mediated effects. Most inhibitors are not reported to have antinociceptive properties, but 2 -deoxycoformycin was proven to have an inhibitory effect on pain transmission (Poon and Sawynok, 1999), and Fujisawa Pharmaceuticals claim adenosine deaminase inhibitors to be active against chronic pain. 

The semisynthesis of avinosol was performed from avarone (8) and 2 -deoxyinosine to confirm the structure of the natural product. Avarone was prepared by oxidation of the naturally occurring avarol (9) obtained in the same extract (Scheme 9.1). 

Similarly, adenosine, inosine and 2 -deoxyinosine have been converted into their 8-trifluoromethyl derivatives by reaction with the copper complex formed from trifluoromethyl iodide and copper in hexamethylphosphorotriamide (80JCS(P1)2755). iV -Trifluoromethyl-purine riboside was also produced from 6-chloropurine riboside. Recently, guanosine has been shown to give the C (8)-substituted derivative (148) by reaction with a benz[a]anthracene 5,6-dioxide at pH 9.5 over 4 days at 37 °C (80CC82). 

While 0-protected guanosine with a free or acylated 2-amino group is selectively 0 -sulfonylated (77CC79I 80TL2265), the 3, 5 -0-acetyl-2 -deoxyinosine, on reaction with TIPS-CI, gives nearly equal amounts of the desired 0 -sulfonylated derivative, which is isolated in only 33% yield, and the corresponding undesired N -sulfonylated derivative (87JA1275). 

De Clercq, E., Stollar, B. D., Hobbs, J., et al. (1980) Interferon induction by two 2 -modi(icd double-helical RNAs, poly(2 -nuoro-2 -deoxymosimc acid) poly(cytidylic acid) and poly(2 -chloro-2 -deoxyinosinic acid) poly(cytidylic acid). Ear. J. Biochem., 107, 279-288. 

It has been demonstrated that it is possible to insert paramagnetic probes into nucleic acids in a site- and type-specific manner. To this end, the 2,2,6,6-tet-ramethyl-l-piperidinyloxy free radical-labelled phosphoramidites of 2-amino-2 -deoxyadenosine, 2 -deoxyadenosine, 2 -deoxycytosine and 5-methyl-2 -deoxycytosine have been prepared and used for the automatic synthesis of mono-labeled oligodeoxynucleotides which proved active by EPR. The phosphoramidites carry a nitroxide spin-label directly linked to the exocyclic amino group. Starting from appropriately protected 2 -deoxyguanosine or 2 -deoxyinosine, the precursors to (66a) and (66b) were obtained by nucleophilic... 

Because of the uncertainties in the intrinsic effects for studies with inosine, because of high commitments, the experiments were repeated with 2 -deoxyinosine, a slow substrate. 

Guanine + D-ribosyl phosphate guanosine -f- phosphate Hypoxanthine + D-ribosyl phosphate inosine + phosphate Hypoxanthine 2-deoxy- D-ribosyl phosphate 2-deoxyinosine + phosphate... 

Figure 12.9 (a) Base sequence contexts investigated, where C represents the 10S (+)-trar)S-or)t/-B[o]P-/ /2-dC adduct in all sequences. The duplex I6C7 is identical to C6C7 except for the designated 2 -deoxyinosine (I). (b) Structures for guanine... 

Deoxyinosine) Adenosine turnover 3.8 Yield to glucose 5.6% Yield to acetaldehyde 17.5% Yield to adenine 83.3%... 

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