title: Trifluoroselenomethionine: A New Unnatural Amino Acid.
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.
authors.affiliation: Department of Chemistry, University at Albany, State University of New York, 1400 Washington Ave., Albany, NY, 12222, USA. eblock@albany.edu.
authors.forename: Eric
authors.identifier: 0000-0002-4668-1687
authors.initials: E
authors.lastname: Block
authors.affiliation: Department of Chemistry, The Pennsylvania State University, 302 Chemistry Building, University Park, PA, 16802, USA.|Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA, 16802, USA.
authors.forename: Squire J
authors.initials: SJ
authors.lastname: Booker
authors.affiliation: Department of Chemistry, University at Albany, State University of New York, 1400 Washington Ave., Albany, NY, 12222, USA.
authors.forename: Sonia
authors.initials: S
authors.lastname: Flores-Penalba
authors.affiliation: Department of Geological Sciences, University of Saskatchewan, 114 Science Place, Saskatoon, Saskatchewan, S7N 5E2, Canada.
authors.forename: Graham N
authors.identifier: 0000-0002-7211-5937
authors.initials: GN
authors.lastname: George
authors.affiliation: Department of Chemistry, University at Albany, State University of New York, 1400 Washington Ave., Albany, NY, 12222, USA.
authors.forename: Sivaji
authors.initials: S
authors.lastname: Gundala
authors.affiliation: Department of Chemistry, The Pennsylvania State University, 302 Chemistry Building, University Park, PA, 16802, USA.
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Landgraf
authors.affiliation: Department of Chemistry and Biochemistry, University of Delaware, 163 The Green, Newark, DE, 19716, USA.
authors.forename: Jun
authors.identifier: 0000-0003-1766-0411
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Chemistry, University at Albany, State University of New York, 1400 Washington Ave., Albany, NY, 12222, USA.
authors.forename: Stephene N
authors.initials: SN
authors.lastname: Lodge
authors.affiliation: Department of Geological Sciences, University of Saskatchewan, 114 Science Place, Saskatoon, Saskatchewan, S7N 5E2, Canada.|College of Medicine, University of Saskatchewan, 107 Wiggins Road, Saskatoon, Saskatchewan, S7N 5E5, Canada.
authors.forename: M Jake
authors.initials: MJ
authors.lastname: Pushie
authors.affiliation: Department of Chemistry and Biochemistry, University of Delaware, 163 The Green, Newark, DE, 19716, USA. rozovsky@udel.edu.
authors.forename: Sharon
authors.identifier: 0000-0003-4902-0777
authors.initials: S
authors.lastname: Rozovsky
authors.affiliation: Department of Chemistry, University at Albany, State University of New York, 1400 Washington Ave., Albany, NY, 12222, USA.|Department of Bioorganic Chemistry, Max Planck Institute for Chemical Ecology, Hans Knoll Strasse 8, 07745, Jena, Germany.
authors.forename: Abith
authors.initials: A
authors.lastname: Vattekkatte
authors.affiliation: Department of Chemistry, University at Albany, State University of New York, 1400 Washington Ave., Albany, NY, 12222, USA.|Atlanta Metropolitan State College, 1630 Metropolitan Parkway SW, Atlanta, GA, 30310, USA.
authors.forename: Rama
authors.initials: R
authors.lastname: Yaghi
authors.affiliation: United States Department of Agriculture, Agricultural Research Service, Grand Forks Human Nutrition Research Center, 2420 2nd Avenue North, Grand Forks, ND, 58203, USA.
authors.forename: Huawei
authors.initials: H
authors.lastname: Zeng
mesh_terms: D000596:Amino Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013437:Carbon-Sulfur Lyases / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D045325:HCT116 Cells; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D011789:Quantum Theory; D012645:Selenomethionine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000596:Amino Acids; C000621939:trifluoroselenomethionine; D012645:Selenomethionine; D013437:Carbon-Sulfur Lyases; C021558:L-methionine gamma-lyase
keywords: amino acids; fluorine; methionine gamma-lyase; selenomethionine; trifluoroselenomethionine