SYNTHESIS AND PROPERTIES OF NUCLEOSIDE 5'-PHOSPHOAZIDATES DERIVED FROM GUANOSINE AND ADENOSINE NUCLEOTIDES - EFFECT ON ELONGATION FACTORS-G AND FACTOR-TU DEPENDENT REACTIONS
SYNTHESIS AND PROPERTIES OF NUCLEOSIDE 5'-PHOSPHOAZIDATES DERIVED FROM GUANOSINE AND ADENOSINE NUCLEOTIDES - EFFECT ON ELONGATION FACTORS-G AND FACTOR-TU DEPENDENT REACTIONS
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DOI：
10.1021/bi00638a029
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发表时间：
1977-01-01
期刊：
影响因子：
2.9
通讯作者：
OFENGAND, J
中科院分区：
文献类型：
--
作者：
CHLADEK, S;QUIGGLE, K;OFENGAND, J
通过叠氮离子对相应的活化核苷进行亲核取代，合成了一种新型的核苷聚（5“-磷酸）类似物--核苷5”-磷酸叠氮酯，它在GTP、ATP、GDP、GMP和AMP的末端磷酸上具有叠氮基，产率为25- 45%。鸟苷5“-叠氮磷酸容易被UV光光解;相应的腺苷衍生物光解更慢。鸟苷5“-O-（2-叠氮基二磷酸）和鸟苷5”-O-（3-叠氮基三磷酸）是核糖体-EF-G [延伸因子G]-GDP-梭链孢酸复合物和核糖体-EF-G GT3形成的竞争性抑制剂。前一种反应的Kd分别计算为27和7 μ M，或GDP的270和73倍。在不存在夫西地酸的情况下进行的后一反应中，Ki [抑制常数]值分别为330和28 μ M，或GDP的12倍和1倍。鸟苷5“-O-（2-叠氮基二磷酸）和鸟苷5”-O-（3-叠氮基三磷酸）也与GTP竞争形成二元复合物。EF-Tu-GTP，相对于GTP的Kd值分别为750和75。[延伸因子和核糖体来自大肠杆菌]。
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].