Photo-Claisen Rearrangement in a Coumarin-Caged Peptide leads to a Surprising Enzyme Hyperactivation.
Chembiochem
; : e202400561, 2024 Aug 22.
Article
de En
| MEDLINE
| ID: mdl-39172538
ABSTRACT
Protein phosphatase-1 (PP1) is a ubiquitous enzyme counteracting hundreds of kinases in cells. PP1 interacts with regulatory proteins via an RVxF peptide motif that binds to a hydrophobic groove on the enzyme. PP1-disrupting peptides (PDPs) compete with these regulatory proteins, leading to the release of the active PP1 subunit and promoting substrate dephosphorylation. Building on previous strategies employing the ortho-nitrobenzyl (o-Nb) group, we introduced coumarin derivatives into a PDP via an ether bond to explore their effects on PP1 activity. Surprisingly, our study revealed that the coumarin-caged peptides (PDP-DEACM and PDP-CM) underwent a photo-Claisen rearrangement, resulting in an unexpected hyperactivation of PP1. Our findings underscore the importance of linker design in controlling uncaging efficiency and highlight the need for comprehensive in vitro analysis before cellular experiments.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Langue:
En
Journal:
Chembiochem
Sujet du journal:
BIOQUIMICA
Année:
2024
Type de document:
Article
Pays d'affiliation:
Allemagne
Pays de publication:
Allemagne