Gesellschaft Deutscher Chemiker
Keine Benachrichtigungen
Sie haben noch keine Lesezeichen
Abmelden

Artikel

3‐Chloro‐5‐substituted‐1,2,4‐thiadiazoles (TDZs) as selective and efficient protein thiol modifiers

Von Wiley-VCH zur Verfügung gestellt

The study of cysteine modifications has gained a lot of attention in the last years. This includes detailed investigations in the field of redox biology with focus on numerous redox derivatives like nitrosothiols, sulfenic acids, sulfinic acids and sulfonic acids resulting from increasing oxidation, S-lipidation, and perthiols. For these studies selective and rapid blocking of free protein thiols is required to prevent disulfide rearrangement. In our attempt of finding new inhibitors of human histone deacetylase 8 (HDAC8) we discovered 5sulfonyl and 5-sulfinyl substituted 1,2,4-thiadiazoles (TDZ), which surprisingly show an outstanding reactivity against thiols in aqueous solution. Encouraged by these observations we investigated the mechanism of action in detail and showed that these compounds react more specific and faster than commonly used N-ethyl maleimide making them superior alternatives for efficient blocking of free thiols in proteins. We show that 5-sulfonyl-TDZ can be readily applied in commonly used biotin switch assays. And at the example of human HDAC8 we demonstrate that cysteine modification by a 5-sulfonyl-TDZ can be readily applied in commonly used biotin switch assays. And at the example of human HDAC8 we demonstrate that cysteine modification by a 5-sulfonyl-TDZ is easily measurable using quantitative HPLC/ESI-QTOF-MS/MS, and even allows for the simultaneous measurement of the modification kinetics of seven solvent accessible cysteines in HDAC8.

Zum Volltext

Überprüfung Ihres Anmeldestatus ...

Wenn Sie ein registrierter Benutzer sind, zeigen wir in Kürze den vollständigen Artikel.