POTENT INHIBITORS OF THE PLASMODIUM PROTEASOME AND THEIR SYNTHESIS VIA A NOVEL ROUTE
Researchers at UCSF have developed a novel treatment for the causative pathogens for both malaria and tuberculosis respectively.
Tuberculosis and malaria are caused by different infectious organisms, but both remain major global infectious diease health threats. As these pathogens become more resistant to existing treatments, it is likely that infections will become more common and harder to cure. Both organisms depend on a protein-cleaning system, called the 20S proteasome subunit, to survive stressful conditions inside the human body. However, designing drugs that block this system is challenging because similar machinery exists in human cells and must be spared. This creates an urgent need for new treatments that can precisely target these pathogens without harming the patient.
Stage of Research
This invention comprises a novel treatment for the causative pathogens for tuberculosis as well as malaria. Specifically, the inventors have discovered that syringolins and syringolin-like compounds are successful in inhibiting both of these pathogens. Syringolins are small peptide-like molecules with a reactive group that allows it to bind irreversibly to the proteasome. This in turn blocks the proteasome which is the cell’s protein “recycling” system and is a key part of protein degradation and quality control. Syringolins and syringolin-like compounds in this invention have been shown to specifically inhibit the 20S proteasome subunit which is vital for proteasome function. Studies in cell cultures have shown that these compounds can also enhance the efficacy of known tuberculosis treatments such as pretomanid.
Applications
Advantages
Stage of Development
Research- in vitro
Technology Reference
CZ Biohub ref. no. CZB-345F
UCSF ref. no. SF2026-013
Keywords
Malaria, infectious disease