Patent · US Active

Synthetic substrates for enzymes that catalyze reactions of modified cysteines and related methods

US10413583B2 · kind B2 · utility

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13Claims
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Key dates

Filing dateNov 30, 2017
Grant dateSep 17, 2019
Priority date
Expiry dateNov 30, 2037

Classification

  • Technology area (CPC C)Chemistry; Metallurgy
  • CPC primaryC07K5/06086
  • WIPO fieldPharmaceuticals
  • WIPO sectorChemistry

Abstract

Synthetic probes for detecting the activity of enzymes that catalyze reactions of post-translationally modified cysteine residues are described. The probes include “turn-on” probes that include a carbamate linkage that is cleaved via an intramolecular reaction with a free thiol produced by an enzyme catalyzed activity. The probes also include ratiometric, Michael addition-based probes that respond to enzymatic activity by a change in structure that results in a change in fluorescence properties. Methods of using the probes to detect enzymatic activity and disease are described. For example, the probes can be used to detect enzymatic activity in a variety of samples, including live cells and heterogeneous tissues. In addition, prodrugs that can be activated by enzymes that catalyze reactions of post-translationally modified cysteine residues and methods of using the prodrugs to treat disease are described.

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