2 -Deoxyadenosine- 5 -

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... 

Amino-2 -deoxypurines. 2 -AmiQo-2 -deoxyadenosine (15) is a naturally occurring A[-nucleoside isolated from A.ctinomadura that shows antknycoplasmal activity (1,4). Adenosine is the direct precursor for its biosynthesis (30). 2 -Arnino-2 -deoxyguanosine (16), isolated from a strain of Enterobacter cloacae (1,4), shows the growth of HeLa S3 cells and Sarcoma 180 in vivo and has been tested for antibacterial activity. 

Amino-3 -deoxyadenosine. 3 -Amino-3 -deoxyadenosine (17) is elaborated by Cordyceps militarise Aspergillus nidulanSe and Helminthosporium (3,4). The biosynthesis proceeds direcdy from adenosine. Compound (17) inhibits RNA polymerase, but not DNA polymerase, and replaces the adenosyl residue at the 3 -terminus of tRNA. Phenylalanyl-(3 -amino-3 -deoxyadenosyl)-tRNA has acceptor but not donor activity (31,32). Compound (17) also inhibits retroviral RNA-dependent DNA polymerase (33). 

The consequence of ADA deficiency is accumulation of adenosine and 2 -deoxyadenosine, substances toxic to lymphocytes, important cells in the immune response. 2 -Deoxyadenosine is particularly toxic because its presence leads to accumulation of its nucleotide form, dATP, an essential substrate in DNA synthesis. Elevated levels of dATP actually block DNA replication and cell division by inhibiting synthesis of the other deoxynncleoside 5 -triphosphates (see Chapter 27). Accumulation of dATP also leads to selective depletion of cellular ATP, robbing cells of energy. Children with ADA SCID fail to develop normal immune responses and are susceptible to fatal infections, unless kept in protective isolation. 

Deoxyuridine, thymidine, 2 -deoxyadenosine, 2 -deoxycyti-dine, 2 -deoxyguanosine... 

Pentostatin (deoxycoformycin Fig. 4) is a purine isolated from cultures of Streptomyces antibioticus. Its mode of action involves inhibition of adenosine deaminase, which plays a key role in purine salvage pathways and DNA synthesis. As a consequence, deoxyadenosine triphosphate (dATP) is accumulated, which is highly toxic to lymphocytes. This is associated with augmented susceptibility to apoptosis, particularly in T cells. 

S-(5 -Deoxyadenosin-5 -yl)-L-methionine (AdoMet) S-[(1-Adenin-9-yl)-1,5-dideoxy-p-D-ribofuranos-5-yl]-L-methionine [trivial name S-adenosylmethionine (SAM)]... 

RN 29908-03-0 MF CijHjjNgOsS MW 398.44 EINECS 249-946-8 CN 5 -[[(35)-3-amino-3-carboxypropyl]methylsulfonio]-5 -deoxyadenosine inner salt... 

CN cobinamide Co-(5 -deoxyadenosine-5 ) de riv. hydroxide dihydrogen phosphate (ester) inner salt 3 -ester with 5,6-dimethyl-1 -a-D-ribofuranosyl-1 //-benzimidazole... 

A method has been reported for the quantification of the DNA oxidation products, 8-hydroxy-2 -deoxyguanosine (8-OH-dG), 8-hydroxy-2 -deoxyadenosine (8-OH-dA), 5-hydroxymethyl-2-deoxyuridine (HMDU), thymidine glycol (TG) and 2-hydroxy-2 -deoxyadenosine (2-OH-dA) [37], The HPLC system employed consisted of a 2.0 X 250 mm Cig column and gradient elution from waterimethanol, (94 6) to (10 90) over 28 min, at a flow rate of 200 tilmin ... 

Adenosine kinase catalyzes phosphorylation of adenosine and deoxyadenosine to AMP and dAMP, and de-oxycytidine kinase phosphorylates deoxycytidine and 2 -deoxyguanosine to dCMP and dGMP. 

While mammahan cells reutilize few free pyrimidines, salvage reactions convert the ribonucleosides uridine and cytidine and the deoxyribonucleosides thymidine and deoxycytidine to their respective nucleotides. ATP-dependent phosphoryltransferases (kinases) catalyze the phosphorylation of the nucleoside diphosphates 2 "-de-oxycytidine, 2 -deoxyguanosine, and 2 -deoxyadenosine to their corresponding nucleoside triphosphates. In addition, orotate phosphoribosyltransferase (reaction 5, Figure 34-7), an enzyme of pyrimidine nucleotide synthesis, salvages orotic acid by converting it to orotidine monophosphate (OMP). 

Figure 35-3. Base pairing between deoxyadenosine and thymidine involves the formation of two hydrogen bonds. Three such bonds form between deoxycytidine and deoxyguanosine.The broken lines represent hydrogen bonds.

N3-Alkyladenine nucleosides can also undergo ring opening under basic conditions. At pH 8.98, the ring-opening reaction of 3-methyl-2 -deoxyadenosine is... 

The analogons deamination reaction is not observed in l-methyl-2 -deoxy-adenosine nncleosides. ° Rather, in the adenine series, the Dimroth rearrangement occnrs (Scheme 8.4). On the contrary, in styrene adducts of 2 -deoxyadenosine, the hydroxyl residue of the adduct undergoes intramolecular reaction with the base to initiate deamination (Scheme 8.6). ° ° Similarly, cytosine residues bearing styrene adducts at the N3-position undergo rapid deamination (nearly complete deamination is seen within 75h). °°... 

Palom, Y. Lipman, R. Musser, S. M. Tomasz, M. A mitomycin-A-6-deoxyadenosine adduct isolated from DNA. Chem. Res. Toxicol. 1998, 11, 203-210. 

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