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Validation of l ‐Tellurienylalanine as a Phenylalanine Isostere
Author(s) -
Vurgun Nesrin,
Nitz Mark
Publication year - 2020
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201900635
Subject(s) - isothermal titration calorimetry , isostere , rnase p , circular dichroism , chemistry , stereochemistry , context (archaeology) , mass cytometry , peptide , biochemistry , peptidomimetic , dissociation constant , phenylalanine , tripeptide , biophysics , amino acid , biology , rna , paleontology , receptor , gene , phenotype
Abstract Mass cytometry (MC) and imaging mass cytometry (IMC TM ) 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 TM probes.