MIAMI.- Researchers at the University of California in Riverside, United States, found a way to stop MYC, the formless protein responsible for the worsening of most cases of cancer human, which opens up hope for a new era of treatments.
In healthy cells, MYC helps guide the transcription process, in which genetic information is converted from DNA to RNA and, ultimately, proteins. “Normally, MYC activity is strictly controlled. In cancer cells, it becomes overactive and is not properly regulated,” explains Min Xue, associate professor of Chemistry at UCR.
“MYC is less like food for cancer cells and more like a steroid that promotes rapid cancer growth,” Xue said. “That’s why MYC is to blame for 75 percent of all human cancer cases,” she said.
At the beginning of this project, the UCR research team believed that if they could dampen the hyperactivity of MYC, they could open a window in which to control cancer.
However, finding a way to control MYC was challenging because, unlike most other proteins, MYC has no structure. “Basically, it’s a bunch of randomness,” Xue explains. “Conventional drug discovery pathways rely on well-defined structures, and this does not exist for MYC,” she noted.
A new article published in the Journal of the American Chemical Society, of which Xue is lead author, describes a peptide compound that binds to MYC and suppresses its activity. In 2018, researchers noted that changing the stiffness and shape of a peptide improves its ability to interact with unstructured protein targets, such as MYC.
“Peptides can assume a variety of shapes, shapes and positions,” Xue said. “Once you bend them and connect them to form rings, they can’t take on other possible shapes, so they then have a low level of randomness. This helps with bonding,” she explained.
In the paper, the team describes a new peptide that binds directly to MYC with what is called submicro-molar affinity, which approaches the strength of an antibody. In other words, this is a very strong and specific interaction.
“We have improved the binding performance of this peptide by two orders of magnitude over previous versions,” says Xue. “This brings it closer to our drug development goals.”
Currently, researchers use lipid nanoparticles to deliver the peptide into cells. These are small spheres made up of fatty molecules, and are not ideal for use as a drug. Looking ahead, researchers are developing chemistry that improves the lead peptide’s ability to enter cells.
Once inside the cell, the peptide will bind to MYC, modifying its physical properties and preventing it from carrying out transcription activities.
Xue’s lab at UC Riverside develops molecular tools to better understand biology and uses that knowledge to conduct drug discovery. He has long been interested in the chemistry of chaotic processes, which attracted him to the challenge of ‘taming’ MYC.
“MYC represents chaos, basically, because it lacks structure. That and its direct impact on so many types of cancer make it one of the holy grails of cancer drug development,” says Xue. “We are excited that it is now within our reach,” she celebrated.
Source: Europa Press
