Unique peptides with anticancer potential discovered

A group of researchers has discovered a unique type of peptide that can help treat cancer.

In a study recently published in Nature Communicationsthe team noted that the peptides contain no more than a few dozen amino acidsin contrast to proteins, which typically contain hundreds.

The recently discovered cyclic peptides have the ability to bind to ubiquitin protein chains, often used as a “death tag” for damaged proteins. These proteins are then broken down in the proteasome, a cellular structure responsible for removing waste.

THE discovery of the ubiquitin system led to the award of the Nobel Prize of Chemistry 2004 to researchers Aharon Ciechanover, Avraham Hershko and Bruce Rappaport.

Over the years, it has become clear that the activity of the ubiquitin system depends on the point at which molecules are attached to each other in the chain. For example, linking ubiquitin in the strand at position 48 (K48) leads to protein removal, whereas linking at position 63 (K63) leads to repair of damaged DNA.

In recent years, researchers at the Technion – Israel Institute of Technology have developed a new approach to influencing ubiquitin mechanisms. Instead of interfering with the activity of enzymes that affect these mechanisms, they decided to intervene directly in the ubiquitin chain itself.

Based on this approach, they developed cyclic peptides that bind to ubiquitin chains at position K48, preventing them from breaking down damaged proteins. This disruption gradually leads to programmed cell death.

In the same study, they proved that when such an event turns into a malignant tumor, these peptides kill the cancer cells, protecting the patient. This discovery was published in 2019 in the journal Nature Chemistry.

In the current study, cyclic peptides were discovered that bind to the chains connected to position 63 of ubiquitin and are involved in repairing damaged DNA. The researchers found that when linked to these ubiquitin chains, such peptides disrupt the aforementioned repair mechanism.

This leads to accumulation of damaged DNA and cell death. When this binding occurs in cancer cells, they are destroyed.

The researchers believe that this therapeutic strategy could be more effective than existing anticancer drugs, against which patients gradually develop resistance.