Asset Details
Do you wish to reserve the book?
Homo-BacPROTAC-induced degradation of ClpC1 as a strategy against drug-resistant mycobacteria
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Homo-BacPROTAC-induced degradation of ClpC1 as a strategy against drug-resistant mycobacteria
Do you wish to request the book?
Homo-BacPROTAC-induced degradation of ClpC1 as a strategy against drug-resistant mycobacteria
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Homo-BacPROTAC-induced degradation of ClpC1 as a strategy against drug-resistant mycobacteria
2024
Overview
Antimicrobial resistance is a global health threat that requires the development of new treatment concepts. These should not only overcome existing resistance but be designed to slow down the emergence of new resistance mechanisms. Targeted protein degradation, whereby a drug redirects cellular proteolytic machinery towards degrading a specific target, is an emerging concept in drug discovery. We are extending this concept by developing proteolysis targeting chimeras active in bacteria (BacPROTACs) that bind to ClpC1, a component of the mycobacterial protein degradation machinery. The anti-
Mycobacterium tuberculosis
(
Mtb
) BacPROTACs are derived from cyclomarins which, when dimerized, generate compounds that recruit and degrade ClpC1. The resulting Homo-BacPROTACs reduce levels of endogenous ClpC1 in
Mycobacterium smegmatis
and display minimum inhibitory concentrations in the low micro- to nanomolar range in mycobacterial strains, including multiple drug-resistant
Mtb
isolates. The compounds also kill
Mtb
residing in macrophages. Thus, Homo-BacPROTACs that degrade ClpC1 represent a different strategy for targeting
Mtb
and overcoming drug resistance.
Antimicrobial resistance is a global health threat and the development of alternative strategies to overcome it is of high interest. Here, the authors report proteolysis targeting chimeras active in bacteria (BacPROTACs) that bind to ClpC1, a component of the mycobacterial protein degradation machinery, and apply them for targeting a range of mycobacterial strains, including antibiotic-resistant ones.
