8-Azaguanine 8-Azaguanylate

Azaguanine was the first purine analogue shown to be incorporated into polynucleotides [337] and, since its primary metabolic effect is on protein synthesis, the incorporation into RNA is considered the basis for its biologic activity [338]. In microbial systems 8-aza-adenine, 8-azahypoxanthine, 8-azaxanthine, and 5(4)-amino-l/f-l, 2, 3-triazole-4(5)-carboxamide are all incorporated into RNA as 8-azaguanylic acid [336]. 

One of the first demonstrations that acquired resistance could be circumvented was the inhibition of 5. faecalis resistant to 8-azaguanine by 8-azaxanthine. Thus, cells that possess xanthylic acid phosphoribosyltransferase activity could form 8-azaxanthylic acid, which was then converted to 8-azaguanylic acid and incorporated in nucleic acids as such [98]. 

The directed synthesis of Bis-group compounds by the E. coli-Factor B system has some resemblance to the incorporation of 8-aza-guanine into the nucleic acid of the tobacco mosaic virus, as proved by the isolation of 8-azaguanylic acid from the nucleic acid (Matthews, 1954). Inhibition by 8-azaguanine is attributable to the inability of the virus particles to multiply when they contain 8-azaguanine in their nucleic acid. 

In conclusion, an absolute prerequisite for 8-azaguanine activity in cells is this possibility to be transformed into azaguanylic acid. The analogue is incorporated into nucleic acids (especially RNA). but since the cofactor GTP is. in addition, very important in the mechanism of translation, it might be supposed that when Aza GTP replaces GTP. this mechanism may be impaired. 

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