Title | Validation of l-Tellurienylalanine as a Phenylalanine Isostere. |
Publication Type | Journal Article |
Year of Publication | 2020 |
Authors | Vurgun, N, Nitz, M |
Journal | Chembiochem |
Volume | 21 |
Issue | 8 |
Pagination | 1136-1139 |
Date Published | 2020 Apr 17 |
ISSN | 1439-7633 |
Abstract | Mass cytometry (MC) and imaging mass cytometry (IMC ) have emerged as important tools for the study of biological heterogeneity. We recently demonstrated the use of l-2-tellurienylalanine (TePhe), a mimic of phenylalanine (Phe), as an MC- and IMC-compatible protein synthesis reporter. In this work, the biochemical similarity of TePhe and its cognate analogue, Phe, are examined in the context of the RNase S complex. Isothermal titration calorimetry studies show that incorporation of TePhe preserves the interaction of S-peptide with S-protein, and the dissociation constants for the interaction of the Phe and TePhe peptides are within a factor of two. The resulting RNase S complex is catalytically active without significant alterations in the enzyme's kinetic parameters. Furthermore, circular dichroism spectroscopy does not reveal any changes to the secondary structure of TePhe-substituted RNase S. These findings provide strong evidence that TePhe functions as a Phe isostere in the context of a folded protein. It is anticipated that incorporation of TePhe into peptides or peptidomimetic scaffolds will enable facile generation of MC and IMC probes. |
DOI | 10.1002/cbic.201900635 |
Alternate Journal | Chembiochem |
PubMed ID | 31742805 |
Grant List | RGPIN-2016-06 / / Natural Sciences and Engineering Research Council of Canada / |