Unique peptides with potential anti-cancer capabilities have been found by Technion and University of Tokyo scientists. Unusual peptides have the potential to be effective anti-cancer agents, according to a recent study published in Nature Communications.
Attention has been drawn to peptides because of their possible application in the treatment of cancer. Peptides are little chains of amino acids joined together by peptide bonds.
Peptides only have a few dozens of amino acids, as opposed to proteins, which typically have hundreds. The cyclic peptides were found to particularly link to ubiquitin protein chains. These are often utilized as a “death tag” for damaged proteins.
These marked proteins are then broken down in the proteasome, a cellular structure responsible for removing waste.
It became evident through time that the location of the ubiquitin molecules’ connections to one another in the chain plays a role in the ubiquitin system’s ability to function.
For instance, joining the ubiquitin at position 48 (K48) in the chain results in the removal of proteins to the proteasome. However, linking the ubiquitin at position 63 (K63) results in the repair of damaged DNA.
Technion Scientists: Peptides — A New Laser Against Cancer
Technion researchers have created a new approach for manipulating the ubiquitin processes recently. They chose to try direct intervention in the ubiquitin chain rather than affecting the activity of enzymes that influence these pathways.
Based on this approach, the researchers created cyclic peptides in a prior study. These bind the K48-linked ubiquitin chains and stop them from causing the breakdown of the damaged proteins. Cells progressively begin to die as intended as a result of this disruption.
They proposed and subsequently demonstrated in the same study that when such an event developed in a malignant tumor, it killed the cancer cells, potentially protecting the patient.
This discovery, which was reported on in the 2019 issue of the journal Nature Chemistry, sparked the creation of a brand-new startup that is moving the discovery closer to clinical use.
The current study identified cyclic peptides that are important in mending damaged DNA. Also, it binds the chains related to position 63 in ubiquitin. The scientists discovered that these peptides interfere with the aforementioned repair mechanism when bound to these ubiquitin chains.
Cell death results from this and the accumulation of damaged DNA. Again, when this binding takes place in cancer cells, it kills those cells. According to the researchers, this therapeutic approach may be more successful. That is, more successful than the currently available anti-cancer medications, to which patients gradually develop resistance.
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Professor Ashraf Brik, Dr. Ganga B. Vamisetti, and Dr. Abbishek Saha from the Technion’s Schulich Faculty of Chemistry collaborated on the study with Professor Nabieh Ayoub from the Technion’s Faculty of Biology and Professor Hiroaki Suga from the University of Tokyo.