Trifluoroselenomethionine

A New Unnatural Amino Acid

Eric Block, Squire J. Booker, Sonia Flores-Penalba, Graham N. George, Sivaji Gundala, Bradley J. Landgraf, Jun Liu, Stephene N. Lodge, M. Jake Pushie, Sharon Rozovsky, Abith Vattekkatte, Rama Yaghi, Huawei Zeng

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1738-1751
Number of pages14
JournalChemBioChem
Volume17
Issue number18
DOIs
StatePublished - Sep 15 2016

Fingerprint

Selenomethionine
Amino Acids
Escherichia coli
Methionine
Methionine Adenosyltransferase
HCT116 Cells
Cytotoxicity
Selenium
Aspartic Acid
Discrete Fourier transforms
Colonic Neoplasms
Esters
Proteins
Cells
Cell Line
Substrates

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Organic Chemistry

Cite this

Block, E., Booker, S. J., Flores-Penalba, S., George, G. N., Gundala, S., Landgraf, B. J., ... Zeng, H. (2016). Trifluoroselenomethionine: A New Unnatural Amino Acid. ChemBioChem, 17(18), 1738-1751. https://doi.org/10.1002/cbic.201600266
Block, Eric ; Booker, Squire J. ; Flores-Penalba, Sonia ; George, Graham N. ; Gundala, Sivaji ; Landgraf, Bradley J. ; Liu, Jun ; Lodge, Stephene N. ; Pushie, M. Jake ; Rozovsky, Sharon ; Vattekkatte, Abith ; Yaghi, Rama ; Zeng, Huawei. / Trifluoroselenomethionine : A New Unnatural Amino Acid. In: ChemBioChem. 2016 ; Vol. 17, No. 18. pp. 1738-1751.
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Block, E, Booker, SJ, Flores-Penalba, S, George, GN, Gundala, S, Landgraf, BJ, Liu, J, Lodge, SN, Pushie, MJ, Rozovsky, S, Vattekkatte, A, Yaghi, R & Zeng, H 2016, 'Trifluoroselenomethionine: A New Unnatural Amino Acid', ChemBioChem, vol. 17, no. 18, pp. 1738-1751. https://doi.org/10.1002/cbic.201600266

Trifluoroselenomethionine : A New Unnatural Amino Acid. / Block, Eric; Booker, Squire J.; Flores-Penalba, Sonia; George, Graham N.; Gundala, Sivaji; Landgraf, Bradley J.; Liu, Jun; Lodge, Stephene N.; Pushie, M. Jake; Rozovsky, Sharon; Vattekkatte, Abith; Yaghi, Rama; Zeng, Huawei.

In: ChemBioChem, Vol. 17, No. 18, 15.09.2016, p. 1738-1751.

Research output: Contribution to journalArticle

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T1 - Trifluoroselenomethionine

T2 - A New Unnatural Amino Acid

AU - Block, Eric

AU - Booker, Squire J.

AU - Flores-Penalba, Sonia

AU - George, Graham N.

AU - Gundala, Sivaji

AU - Landgraf, Bradley J.

AU - Liu, Jun

AU - Lodge, Stephene N.

AU - Pushie, M. Jake

AU - Rozovsky, Sharon

AU - Vattekkatte, Abith

AU - Yaghi, Rama

AU - Zeng, Huawei

PY - 2016/9/15

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N2 - 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.

AB - 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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Block E, Booker SJ, Flores-Penalba S, George GN, Gundala S, Landgraf BJ et al. Trifluoroselenomethionine: A New Unnatural Amino Acid. ChemBioChem. 2016 Sep 15;17(18):1738-1751. https://doi.org/10.1002/cbic.201600266