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Compugen announces a new platform for the discovery of peptides that block protein structures associated with diseases

In an initial run, biological effectiveness of the new platform was demonstrated in two drug candidates

Alpha-helix structure of a protein, from Wikipedia
Alpha-helix structure of a protein, from Wikipedia

Compugen announced the development and proof of feasibility of a new discovery platform (Blockers of Disease Associated Conformations). It is a discovery platform for identifying peptides that prevent proteins from adopting a three-dimensional structure associated with diseases. Two of the candidates predicted in the initial run of the platform were tested in the laboratory, and both showed positive results, one anti-inflammatory activity and the other anti-cancer activity.

The new platform was designed to identify segments of proteins that, when added as synthetic peptides, block structural changes of the protein and thus prevent it from adopting a disease-related structure. The platform makes it possible to conduct an extensive search in the human proteome, as well as in the proteomes of viruses and bacteria that cause various diseases.

An initial run of the discovery platform yielded reliable computational prediction of peptide drug candidates for approximately 40 targets for potential use in various diseases, including various cancers, inflammatory diseases, infectious shock, and viral diseases. Seven of these targets were selected for first experimental validation, and inhibitory peptides were found for all of them.

In addition, two of the selected peptides have already shown biological efficacy in experimental disease models. This is proof of both the medicinal potential of the peptides and the reliability of the platform predictions. For example, a single injection of one of the peptides caused a significant reduction in the levels of inflammatory cytokines in the serum of mice in which the immune system was activated in excess by lipopolysaccharide of bacterial origin. In other experimental models, the second peptide showed a reduction in tumorigenesis and an increase in sensitivity to chemotherapeutic agents in breast, colon, and prostate cancer cells. These two peptides are candidates for further testing in additional disease models in animals. Experiments are also planned for additional peptides that have been discovered.

"Preventing disease-related protein structures is an area of ​​pharmaceutical research that depends mainly on experimental discovery methods," said Yossi Cohen, MD, VP of Research and Development at Compugen. "Therefore, we see the new discovery platform as a significant achievement in this field because it replaces a process that is mostly experimental and ineffective, with a computational prediction process, which can be continuously improved, and is combined with experimental verification," continued Dr. Cohen. "The initial results are promising, and we are pleased to add this discovery platform, the ninth we have announced to date, to our expanding infrastructure of discovery capabilities."

On protein folding and structural changes
In order for proteins to function, they need to go through a process called folding to adopt a three-dimensional shape. In addition, many proteins undergo structural changes when they go from an active to an inactive state. In certain proteins, such structural changes are related to the role of the protein in disease states. Therefore, molecules that target and can block the structure of the protein associated with the disease, such as the peptides identified with Compugen's new platform, could have many possible uses in various medical fields.

2 תגובות

  1. The caption of the picture is incorrect - there is no alpha helix protein - that's what the folding of the protein is called, a motif that repeats itself in many proteins

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