New molecule targets key protein in autoimmune diseases.
Posted by giorgiobertin on January 14, 2024
The scientists of the Scripps Research have developed a small molecule that blocks the activity of a protein linked to autoimmune diseases, including systemic lupus erythematosus (SLE) and Crohn’s disease. This protein, known as SLC15A4was considered largely “unshakeable,” as most researchers had long struggled to isolate the protein, determine its structure, or even define its exact function within immune cells.
The research, published in “Nature Chemical Biology“, shows that the compound successfully reduced inflammation in mouse models of inflammation, as well as in isolated cells from people diagnosed with lupus. This provides scientists with a new tool to study the role of SLC15A4 in autoimmunity, as well as a potential new therapy to proceed towards further preclinical studies.
The researchers used this approach to discover nine different molecular fragments that could bind to SLC15A4 proteins within human immune cells. They performed a series of experiments to demonstrate that one of these fragments, FFF-21, physically bound to SLC15A4 and at the same time prevented its function in promoting inflammation. Next, they created modified variants of FFF-21 and identified one, called AJ2-30which showed particularly promising efficacy in blocking SLC15A4 and reducing inflammation in several cell types.
The researchers believe that blocking SLC15A4 could open up new perspectives for the study and treatment of autoimmune diseases.
Read abstract of the article:
Chemoproteomic development of SLC15A4 inhibitors with anti-inflammatory activity.
Chiu, T.-Y., et al. (2024).
Nature Chemical Biology. doi.org/10.1038/s41589-023-01527-8.
Source: Department of Chemistry, The Scripps Research Institute, La Jolla, CA, USA
This entry was posted on gennaio 14, 2024 a 6:34 am and is filed under News-research. Tagged: biochemistry, biology, chemistry, immunology. You can follow any responses to this entry through the RSS 2.0 feed.
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