Trifluoroselenomethionine: A New Unnatural Amino Acid |
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| Authors: | Prof. Eric Block Prof. Squire J. Booker Dr. Sonia Flores‐Penalba Prof. Graham N. George Dr. Sivaji Gundala Dr. Bradley J. Landgraf Jun Liu Dr. Stephene N. Lodge Dr. M. Jake Pushie Prof. Sharon Rozovsky Dr. Abith Vattekkatte Rama Yaghi Dr. Huawei Zeng |
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| Affiliation: | 1. Department of Chemistry, University at Albany, State University of New York, Albany, NY, USA;2. Department of Chemistry, The Pennsylvania State University, University Park, PA, USA;3. Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA, USA;4. Department of Geological Sciences, University of Saskatchewan, Saskatoon, Saskatchewan, Canada;5. Department of Chemistry and Biochemistry, University of Delaware, Newark, DE, USA;6. College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada;7. Department of Bioorganic Chemistry, Max Planck Institute for Chemical Ecology, Jena, Germany;8. Atlanta Metropolitan State College, Atlanta, GA, USA;9. United States Department of Agriculture, Agricultural Research Service, Grand Forks Human Nutrition Research Center, Grand Forks, ND, USA |
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| Abstract: | Trifluoroselenomethionine (TFSeM), a new unnatural amino acid, was synthesized in seven steps from N‐(tert‐butoxycarbonyl)‐l ‐aspartic acid tert‐butyl ester. TFSeM shows enhanced methioninase‐induced cytotoxicity, relative to selenomethionine (SeM), toward HCT‐116 cells derived from human colon cancer. Mechanistic explanations for this enhanced activity are computationally and experimentally examined. Comparison of TFSeM and SeM by selenium EXAFS and DFT calculations showed them to be spectroscopically and structurally very similar. Nonetheless, when two different variants of the protein GB1 were expressed in an Escherichia coli methionine auxotroph cell line in the presence of TFSeM and methionine (Met) in a 9:1 molar ratio, it was found that, surprisingly, 85 % of the proteins contained SeM residues, even though no SeM had been added, thus implying loss of the trifluoromethyl group from TFSeM. The transformation of TFSeM into SeM is enzymatically catalyzed by E. coli extracts, but TFSeM is not a substrate of E. coli methionine adenosyltransferase. |
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| Keywords: | amino acids fluorine methionine gamma-lyase selenomethionine trifluoroselenomethionine |
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