A Chemical Probe for Dehydrobutyrine

Abstract

Supporting information and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.

Bioorthogonal Reactions of Triarylphosphines and Related Analogues

“…Second-order rate constants of selected phosphine reactions with CpO 78. mode of reactivity could enable additional probe attachments or target enrichment. 323,324 The CpO-phosphine reaction is compatible with and orthogonal to several common bioorthogonal transformations. Mutually orthogonal reactions are desirable for simultaneous biomolecule tagging or activation.…”

“…350−352 The phospha-Michael addition has enabled chemical retrieval of α,β-unsaturated carbonyl modifications and numerous profiling experiments. 323 Electron-deficient alkenes are relatively rare elsewhere in the cell. Thus, biomolecule targets purposefully outfitted with α,βunsaturated carbonyl groups can be selectively ligated with detectable probes via phospha-Michael addition.…”

“…To circumvent this issue, high concentrations of the phosphine probe are used to drive product formation. 323,324,343 More nucleophilic trialkylphosphine probes can also favor product formation. 323,324,343,353 For example, tris(2-carboxyethyl)phosphine (TCEP) ligates α,β-unsaturated carbonyls to yield stable phosphonium adducts (100, Scheme 5).…”

“…Phosphines were found to react more readily and have a wider substrate scope than thiol nucleophiles in Michael addition reactions. 323 The scope of the phospha-Michael reaction was recently expanded to 1,1,2-trisubstituted alkenes. Trisubstituted alkenes comprise a number of post-translational modifications.…”

Dehydroamino acid chemical biology: an example of functional group interconversion on proteins

“…1c ) was developed recently to label Dha and Dhb on proteins that were resistant to Michael addition chemistry using reagents containing thiol and amine nucleophiles. 12 Importantly, the probe engaged Dhb-containing proteins such as the MAPK ERK1/2 in cell lysate formed by the action of OspF and showed that the histone H3 is also a target of phospholyase activity. In the future, an unbiased mass spectrometry (MS) proteomic analysis of streptavidin-enriched peptides using the biotinylated probe may reveal additional novel dehydroamino acids in proteins.…”