Deoxy cytidine deamination

Under basic conditions (0.2 M barium hydroxide, 100°, 30 minutes), the nucleoside 3 5 -cycIic phosphates are converted into the 3 - and 5 -phosphates in the ratio of about 5 1. For cytidine 3 5 -cyclic phosphate, some concomitant deamination to the uridine nucleotide analogs is also observed (as noted with cytidine 3 -phosphate), so that the nucleotides obtained are similar to those found in the alkaline hydrolyzate of uridine 3 5 -cyclic phosphate. In addition, one of the nucleotides obtained in these hydrolyzates differs from the 3 - or 5 -phosphates in its ion-exchange chromatographic behavior. The presence of an unidentified nucleoside monophosphate in small proportion was also observed when 2 -deoxy-cytidine 3 5 -cyclic phosphate was hydrolyzed with barium hydroxide under similar conditions. 

The susceptibilities of some of these fluorinated purine nucleosides to the action of enzymes are now described. In contrast to the inertness of the 2 -deoxy-2 -fluoro- and 3 -deoxy-3 -fluorocytidine analogs 739, 744, and 821 towards cytidine deaminase, the adenosine compounds 867, 883, and 906 are readily deaminated - by the adenosine deaminase in erythrocytes and calf intestine, but the resulting (deaminated) inosine compounds (from 867 and 883), as well as 888, are highly resistant - to cleavage by purine nucleoside phosphorylase (to give hypoxanthine base for the first two). The reason was discussed. Both 867 and 883 can form the 5 -triphosphates, without deamination, in human erythrocytes or murine sarcoma cells in the presence of 2 -deoxycoformycin, an adenosine deaminase inhibitor, but... 

Irradiation of cytosine, cytidine, and 2 -deoxycytidine has recently been reported to produce 4,5 -linked dimers (154 R = H, j3-D-ribose, 2-deoxy-/3-D-ribose, respectively) 210 this reaction is accompanied by deamination. Photodimerization (in aqueous solution) of uracil211 and thymine212 affords the 4,6 -linked dimer (155 R = R = H and Me, respectively) the oxetane (156) (probably formed by 1,2-cycloaddition of a triplet carbonyl to an olefinic bond) is proposed as the precursor.212... 

Several pyrimidine deaminases have also been described among which is cytidine deaminase, studied in rabbit liver (31) and in avian blood (33). A deoxy< dine deaminase has been partially purified from extracts of E. coU, which deaminates deoxyqrtidine to form deoxyuridine 2.5 times faster than it does cytidine and is inactive with 5-methylcytoane (34) [Eq. (9)]. This emyme also slowly deaminates hydroxymethylcytosine deoxyriboside to form hydroxymethyluracil deoxyriboside [Eq. (10)], and convert 6-methylcytosine deoxyriboside to thymidine (33) [Eq. (11)]. 

The cytidine and inosine analogues in the 4 -azido-2 -deoxy series were made by well known procedures from the uridine and adenosine analogues, respectively (Scheme II). Thus, following the method of Reese, 4 -azido-2 -deoxyuridine was acetylated and then converted to the 4-triazolide, which on treatment with ammonium hydroxide furnished 4 -azido-2 -deoxycytidine. Using a procedure of Herdewijn, 4 -azido-2 -deoxyadenosine was enzymatically deaminated to the inosine analogue. 

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