title: 5'-β,γ-CHF-ATP diastereomers: synthesis and fluorine-mediated selective binding by c-Src protein kinase.
abstract: 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.
authors.affiliation: †Department of Chemistry and ‡Loker Hydrocarbon Research Institute, University of Southern California, Los Angeles, California 90089, United States.
authors.forename: Candy S
authors.initials: CS
authors.lastname: Hwang
authors.affiliation: †Department of Chemistry and ‡Loker Hydrocarbon Research Institute, University of Southern California, Los Angeles, California 90089, United States.
authors.forename: Alvin
authors.initials: A
authors.lastname: Kung
authors.affiliation: †Department of Chemistry and ‡Loker Hydrocarbon Research Institute, University of Southern California, Los Angeles, California 90089, United States.
authors.forename: Boris A
authors.initials: BA
authors.lastname: Kashemirov
authors.affiliation: †Department of Chemistry and ‡Loker Hydrocarbon Research Institute, University of Southern California, Los Angeles, California 90089, United States.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.affiliation: †Department of Chemistry and ‡Loker Hydrocarbon Research Institute, University of Southern California, Los Angeles, California 90089, United States.
authors.forename: Charles E
authors.initials: CE
authors.lastname: McKenna
mesh_terms: D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000378:metabolism; D003848:Deoxyguanine Nucleotides / Q000737:chemistry*; D005461:Fluorine / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D011485:Protein Binding; D011493:Protein Kinase C / Q000138:chemical synthesis / Q000737:chemistry*; D013237:Stereoisomerism; D019061:src-Family Kinases / Q000737:chemistry*
chemical_list: D003848:Deoxyguanine Nucleotides; D005461:Fluorine; C029603:deoxyguanosine triphosphate; D000255:Adenosine Triphosphate; D019061:src-Family Kinases; D011493:Protein Kinase C