SINTMOL-CIBSint Project Approved in the Brazil Knowledge Program!
The SINTMOL Lab-CIBSint is pleased to announce that the project “Using the PROTAC strategy to degrade COPZ1 and selectively eliminate PDAC cells” has received preliminary approval through the Brazil Knowledge Program!
This is an important idea for the advancement of science, technology, and innovation, notably in oncology, where pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal and difficult types of cancer. The suggested creation of a new therapeutic drug targeting the COPZ1 protein is a significant advance since it directly tackles the shortcomings of current medicines, which frequently lack selectivity and efficacy, resulting in high recurrence and fatality rates.
The Brazilian research laboratory (SINTMOL Lab – CIBSint), located at the Federal University of Mato Grosso do Sul (in Campo Grande, MS) and coordinated by Prof. Adilson Beatriz, will collaborate with the laboratory at North Dakota State University (NDSU), USA, which is coordinated by Brazilian researcher Dr. Roberto da Silva Gomes. In addition, Dr. Eduardo Borges de Melo’s group at UNIOESTE in Cascavel (Paraná) will contribute by undertaking in silico drug design research, with a focus on quantitative structure-activity relationship (QSAR) studies and molecular modeling. This collaborative network will strive to develop novel PROTAC-class medication candidates.
What is a PROTAC?
PROTACs (short for “Proteolysis Targeting Chimeras”) are novel tiny compounds that may kill particular proteins within cells. They function as clever “pointers” that identify undesired or dangerous proteins for removal by the cell’s natural recycling system, the ubiquitin-proteasome system.1
These molecules comprise two primary components, linked by a flexible linker:
1. A component that recognizes the target protein, i.e. the protein that must be removed.
2. Another component that attracts the enzyme E3 ubiquitin ligase, which is part of the cellular breakdown mechanism.
When the PROTAC binds to both the target protein and the E3 ligase, it functions as a “glue”, bringing them together. This causes the target protein to be tagged with a particular identifier known as ubiquitin, indicating that the protein should be transported to the proteasome, a cellular “shredder” that degrades and recycles proteins.
This technique presents a promising approach to treating diseases such as cancer by removing proteins that were previously difficult to target with conventional medications. The versatility in selecting E3 ligases and creating PROTACs allows them to be tuned to certain proteins and situations.
Reference
- Békés, M., Langley, D.R. & Crews, C.M. PROTAC targeted protein degraders: the past is prologue. Nat Rev Drug Discov 21, 181–200 (2022). https://doi.org/10.1038/s41573-021-00371-6