RT Journal Article
SR Electronic
T1 Synthesis and Evaluation of a Stable Isostere of Malonyllysine
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.08.23.263285
DO 10.1101/2020.08.23.263285
A1 Sarah E. Bergholtz
A1 Yihang Jing
A1 Rhushikesh A. Kulkarni
A1 Thomas T. Zengeya
A1 Jordan L. Meier
YR 2020
UL http://biorxiv.org/content/early/2020/08/24/2020.08.23.263285.abstract
AB Lysine malonylation is a recently characterized posttranslational modification involved in the regulation of energy metabolism and gene expression. Two unique features of this posttranslational modification are its negative charge and potential susceptibility to decarboxylation, both of which pose possible challenges to its study. As a step towards addressing these challenges, here we report the synthesis and evaluation of a stable isostere of malonyllysine. First, we find that synthetic substitution of the malonyl group with a tetrazole isostere results in amino acids resistant to thermal decarboxylation. Next, we demonstrate that protected variants of this amino acid are readily incorporated into peptides. Finally, we show that tetrazole isosteres of malonyllysine can be recognized by anti-malonyllysine antibodies, validating their ability to mimic features of the endogenous lysine modification. Overall, this study establishes a new chemical strategy for stably mimicking a metabolite-derived posttranslational modification, providing a foothold for tool development and functional analyses.Competing Interest StatementThe authors have declared no competing interest.