5'-β,γ-CHF-ATP diastereomers: synthesis and fluorine-mediated selective binding by c-Src protein kinase.
5'-β,γ-CHF-ATP diastereomers: synthesis and fluorine-mediated selective binding by c-Src protein kinase.
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DOI：
10.1021/ol503765n
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发表时间：
2015-04-03
期刊：
影响因子：
5.2
通讯作者：
McKenna CE
中科院分区：
文献类型：
--
作者：
Hwang CS;Kung A;Kashemirov BA;Zhang C;McKenna CE
报道了单个β，γ-CHF-ATP立体异构体12 a和12 b的首次制备。仅在C-F氟的取向方面不同，12 a和12 b具有离散的31 P（202 MHz，pH 10.9，ΔδPα 6 Hz，ΔδPβ 4 Hz）和19F NMR（470 MHz，pH 9.8，ΔδF 25 Hz）光谱特征，并表现出对c-Src激酶的IC 50值的6倍差异，这归因于结合12 b的（S）-氟与活性位点中的R388的独特相互作用。
The first preparation of the individual β,γ-CHF-ATP stereoisomers 12a and 12b is reported. Configurationally differing solely by the orientation of the C–F fluorine, 12a and 12b have discrete 31P (202 MHz, pH 10.9, ΔδPα 6 Hz, ΔδPβ 4 Hz) and 19F NMR (470 MHz, pH 9.8, ΔδF 25 Hz) spectral signatures and exhibit a 6-fold difference in IC50 values for c-Src kinase, attributed to a unique interaction of the (S)-fluorine of bound 12b with R388 in the active site.