AI Article Synopsis
- Proteasomes in pathogenic microbes, especially Mycobacterium tuberculosis (Mtb), are being explored as viable targets for new anti-infective drugs due to their ability to help the bacteria resist host defenses.
- Research shows that inhibiting or deleting the Mtb proteasome makes the bacteria more vulnerable to reactive nitrogen species and decreases their survival in host lungs, indicating its potential as a target for anti-Mtb therapies.
- A study developed potent phenylimidazole-based compounds that selectively inhibit Mtb20S by using structure-guided techniques, with X-ray analyses revealing how these compounds specifically interact with mycobacterial proteasomes compared to human ones.
Article Abstract
Proteasomes of pathogenic microbes have become attractive targets for anti-infectives. Coevolving with its human host, (Mtb) has developed mechanisms to resist host-imposed nitrosative and oxidative stresses. Genetic deletion or pharmacological inhibition of the Mtb proteasome (Mtb20S) renders nonreplicating Mtb susceptible to reactive nitrogen species in vitro and unable to survive in the lungs of mice, validating the Mtb proteasome as a promising target for anti-Mtb agents. Using a structure-guided and flow chemistry-enabled study of structure-activity relationships, we developed phenylimidazole-based peptidomimetics that are highly potent for Mtb20S. X-ray structures of selected compounds with Mtb20S shed light on their selectivity for mycobacterial over human proteasomes.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7091493 | PMC |
| http://dx.doi.org/10.1021/acs.jmedchem.9b01187 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!