Incorporation of TePhe into Expressed Proteins is Minimally Perturbing

Abstract

Tellurium is a versatile heavy chalcogen with numerous applications in chemical biology, providing valuable probes in mass cytometry, fluorescence imaging and structural biology. L-Tellurienylalanine (TePhe) is an analogue of the proteinogenic amino acid L-phenylalanine (Phe) in which the phenyl side chain has been replaced by a 5-membered tellurophene moiety. High incorporation level of TePhe in expressed proteins at defined sites is expected to facilitate studies in proteomics, protein NMR spectroscopy, and structure elucidation. As a model we chose immunoglobulin-binding Protein G, B1 domain (GB1) to validate TePhe as a suitable structural analogue for Phe. We demonstrate that approximately 1 in 2 of all Phe sites within GB1 can be substituted with TePhe through expression in standard non-Phe-auxotrophic E. coli in Phe-deficient media containing glyphosate, an inhibitor of aromatic amino acid biosynthesis. The TePhe content of the GB1 sample can be further increased to 85 % through HPLC. Using NMR and CD spectroscopy, we confirm that the Phe-to-TePhe substitution has negligible impact on the global structure and stability of GB1.

Tellurium and Nano-Tellurium: Medicine or Poison?

“…Metabolically, Te is reduced in the liver, methylated into dimethyl tellurium and trimethyl tellurium, and eventually excreted via one’s urine and breath as volatile compounds [ 35 ]. Many studies have investigated the incorporation of Te into proteins and the possible biological role of chalcogenide metal nano-crystals derived from amino acid- and protein-bound Te forms, analogous to those of other sulfur-binding elements [ 77 , 103 , 104 , 105 , 106 ]. Organo-tellurium compounds have antioxidative, protective, or antiproliferative attributes in the cell system [ 107 , 108 , 109 ].…”

A series of potent BODIPY photosensitisers featuring tellurophene motifs at boron

“…17,18,20,21 Indeed, tellurophene, a tellurium-containing heterocycle that is a member of the chalcogenophene family, has been developed as a promising component for small molecule incorporation. 16,19,22…”