Adenophostin A and analogues modified at the adenine moiety: synthesis, conformational analysis and biological activity
Adenophostin A and analogues modified at the adenine moiety: synthesis, conformational analysis and biological activity
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DOI：
10.1039/b415229h
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发表时间：
2005-01-01
影响因子：
3.2
通讯作者：
Potter, BVL
中科院分区：
文献类型：
--
作者：
Borissow, CN;Black, SJ;Potter, BVL
本文报道了腺苷酸A（2）和两个类似物[乙烯基腺苷酸（4）和8-溴腺苷酸（5）]的合成。NMR分析和分子建模的组合被用来比较它们在溶液中的结构，并确定它们都采用非常相似的构象。测试了类似物从表达重组1型大鼠Ins（1，4，5）P3 R的DT 40细胞中动员Ca 2+的能力，这揭示了乙烯基腺苷酸作为Ins（1，4，5）P3 R的高亲和力荧光探针。8-溴代腺苷的效力仅略低。生物学结果支持我们目前关于腺苷A在Ins（1，4，5）P3 R的结合模式的假设，即碱基部分和受体的Arg 504之间的阳离子-π相互作用与H-键合结合可能是腺苷A相对于Ins（1，4，5）P-3的高效力的原因。
The synthesis of adenophostin A (2) and two analogues [etheno adenophostin (4) and 8-bromo adenophostin (5)] modified at the adenine moiety, is reported. A combination of NMR analysis and molecular modelling was used to compare their structures in solution and determined that they all adopt very similar conformations. The analogues were tested for their ability to mobilise Ca2+ from DT40 cells expressing recombinant Type 1 rat Ins(1,4,5) P3R which reveals etheno adenophostin as a high affinity fluorescent probe of the Ins(1,4,5) P3R. 8-Bromo adenophostin was only slightly less potent. The biological results support our current hypothesis regarding the binding mode of adenophostin A at the Ins(1,4,5) P3R, i.e. that a cation-pi interaction between the base moiety and Arg 504 of the receptor in combination with H-bonding may be responsible for the high potency of adenophostin A relative to Ins(1,4,5) P-3.