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5'-?,?-CHF-ATP diastereomers: synthesis and fluorine-mediated selective binding by c-Src protein kinase.

ABSTRACT: The first preparation of the individual ?,?-CHF-ATP stereoisomers 12a and 12b is reported. Configurationally differing solely by the orientation of the C-F fluorine, 12a and 12b have discrete (31)P (202 MHz, pH 10.9, ??P? 6 Hz, ??P? 4 Hz) and (19)F NMR (470 MHz, pH 9.8, ??F 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.

SUBMITTER: Hwang CS

PROVIDER: S-EPMC4892180 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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5'-β,γ-CHF-ATP diastereomers: synthesis and fluorine-mediated selective binding by c-Src protein kinase.

Hwang Candy S CS Kung Alvin A Kashemirov Boris A BA Zhang Chao C McKenna Charles E CE

Organic letters 20150317 7

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 (31)P (202 MHz, pH 10.9, ΔδPα 6 Hz, ΔδPβ 4 Hz) and (19)F 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. ...[more]

PMID: 25781066

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