Scientists Develop Technique To Produce Self-Assembling Anticancer Molecules In Minutes

photo credit: Dr. Cecil Fox/NIH, via Wikimedia Commons.

Scientists from the University of Warwick have developed a simple technique for the production of a variety of self-assembling molecules that could be used to treat both cancer and infection. The small molecules produced, called peptides, work by mimicking the architecture of components of the body’s natural defense system. While the molecules have only been tested in cancer cell lines so far, the results of these studies were promising as they demonstrated both toxicity and selectivity. The work has been published in Nature Chemistry.

Peptides are small molecules naturally found throughout the body that perform a wide range of biological functions. Like proteins, they’re chains of building blocks called amino acids strung together by a type of bond called a peptide bond, but proteins are larger than peptides.

Scientists are interested in these molecules as potential agents to treat infections or cancer, but so far producing them artificially has been costly, difficult to scale-up and also resulted in molecules that behave in an undesirable way. Furthermore, traditional peptides administered as drugs are rapidly neutralized by the body, rendering them useless.

The new technique, pioneered by Professor Peter Scott and colleagues, relies on chemical self-assembly and results in the rapid production of 3D helical molecules. “The chemistry involved is like throwing Lego blocks into a bag, giving them a shake, and finding that you have a model of the Death Star,” Scott said in a news-release. “The design to achieve that takes some thought and computing power, but once you’ve worked it out the method can be used to make a lot of complicated molecular objects.”

Complex self-assembly of big molecules happens all the time in nature, for example in the production of proteins. Developing a technique to trigger this process artificially in the lab without expensive equipment, however, has been a challenge, but the Warwick researchers may have cracked it.

Professor Scott explains that their novel process involves mixing two different organic chemicals, an amino alcohol derivative and a picoline, with iron chloride in a solvent, such as water or methanol. Within minutes, the molecules start to self-assemble, forming strong bonds and folding into a helix. The process is very efficient because the assembly instructions are encoded within the chemical ingredients, negating the need for costly equipment.

After removing the solvent, the scientists are left with peptides in the form of crystals that mimic the active regions of certain defense molecules found naturally in the body. The resulting molecules are helical, positively charged and both water- and fat-loving (amphiphilic).

The researchers have tested these peptides on a human colon cancer cell line and they were found to be highly toxic, but it will be a long time before they can be tested in human trials. That being said, the peptides were also found to be very selective, which is promising.



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