Synthesis and properties of nucleoside 5'-phosphoazidates derived from guanosine and adenosine nucleotides: effect on elongation factors G and Tu dependent reactions

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Abstract
A new type of nucleoside poly(5''-phosphate) analog, nucleoside 5''-phosphoazidate, with an azido group on the terminal phosphate of GTP, ATP, GDP, GMP and AMP was synthesized by nucleophilic displacement of the corresponding activated nucleosides by azide ion in yields of 25-45%. Guanosine 5''-phosphoazidate is readily photolyzed by UV light; the corresponding adenosine derivative photolyzes more slowly. Guanosine 5''-O-(2-azidodiphosphate) and guanosine 5''-O-(3-azidotriphosphate) are competitive inhibitors of the formation of the ribosome-EF-G[elongation factor G]-GDP-fusidic acid complex and of the ribosome-EF-G GTPase. The Kd of the former reaction are calculated to be 27 and 7 .mu.M, respectively, or 270 and 73 times that of GDP. In the latter reaction, which is conducted in the absence fo fusidic acid, the Ki [inhibition constant] values are 330 and 28 .mu.M, respectively, or 12 and 1 times that of GDP. Guanosine 5''-O-(2-azidodiphosphate) and guanosine 5''-O-(3-azidotriphosphate) also compete with GTP in the formation of the binary complex. EF-Tu-GTP, with respective Kd values of 750 and 75 relative to GTP. [Elongation factors and ribosomes are from Escherichia coli].

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