Regioselective rapid ene-type reaction (RRER) enables bioconjugation of histone serotonylation.

ABSTRACT: Triazolinedione (TAD) derivatives have been commonly utilized as protection and labeling reagents for indole and phenol moieties via a reversible ene-type reaction. Previous studies showed that the TAD probes could selectively modify tyrosine and tryptophan side-chains within proteins and peptides under distinct pH conditions. Here, we report a pH-controlled regioselective rapid ene-type reaction (RRER) between TAD and 5-hydroxyindole, where the modification occurs on the C4 position rather than the C3 of inactivated indole rings. Employing this unique reaction, we have performed the selective bioconjugation of serotonylation occurring on the fifth amino acid residue, glutamine, of histone H3 (H3Q5), which does not contain any tryptophan in its protein sequence. Finally, RRER was ap

SUBMITTER: Wu J 

PROVIDER: S-EPMC12282475 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature