Stability of a Multiresponsive Sulfonium Vinyl Sulfide Linker toward Nucleophilic/Radical Thiols, Reactive Nitrogen Species, and in Cells under Pro-inflammatory Stimulation.
Biomacromolecules
; 25(9): 6017-6025, 2024 Sep 09.
Article
em En
| MEDLINE
| ID: mdl-39166922
ABSTRACT
Chemical linkages that respond to biological stimuli are important for many pharmaceutical and biotechnological applications, making it relevant to explore new variants with different responsivity profiles. This work explores the responsiveness of a TAT peptide-based sulfonium vinyl sulfide probe that responds to nucleophilic thiols, radical thiol species (RTS), and reactive nitrogen species (RNS). Under model conditions, response to nucleophilic thiols was very slow (hours/days), though fast with down to molar equivalents of either RTS or RNS (minutes). These reactions led to the traceless release of a methionine-containing peptide in the first two cases and to a hydroxy nitration adduct in the third case. Despite the sensitive nature of the probe, it remained stable for at least â¼2 h in the presence of cells during TAT-mediated trafficking, even under pro-inflammatory stimulation. The thiol-responsiveness is intermediate to that observed for disulfide linkers and conventional cysteine-maleimide linkers, presenting opportunities for biotechnological applications.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Compostos de Sulfidrila
/
Espécies Reativas de Nitrogênio
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article