Metabolism of Purine Nucleoside Analog&
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چکیده
ducing carcinostasis, with tumor cells resistant to thio guanine, has been suggested (9). The aand @9-anomers of 2'-deoxythioguanosine (TGDR) have been shown to be active against ascites tumors having either of two types of resistance to thioguanine (10). The kinases necessary for conversion of these nucleosides to nucleotides were apparently present in the tumor cell lines examined. How ever, the effectiveness of TGDR against the tumors was found to be limited because of an unfavorable ratio in the two activities : nucleoside cleavage and phosphorylation of nucleoside to nucleotide. This problem is not limited to the use of thioguanosines for carcinostasis, but is involved in the use of other fraudulent nucleosides for tumor therapy. Birnie et o2. (1) studied the cleavage of 5-fluoro 2'-deoxyuridine and attempted to find inhibitors of the reaction. Welch and Prusoff (15) observed the same limitation in the use of 5-iodo-2'-deoxyuridine. This report describes a number of experiments conducted to determine the effects of structural modifications on the cleavage of nucleosides. Some of the adenine nucleosides included in the investigation were substrates for adenosine deaminase. Studies concerning the activity and catabo lism of these adenine nucleosides are included.
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