Enzymes as Anticancer Therapeutic Agents

A team of US researchers has created a new form of an enzyme that has the capability of producing a range of potential new therapeutic agents with anticancer and antibiotic properties.

The novel enzyme create new agents to treat cancer and fight infection and is capable of changing the chemical properties of a variety of existing drugs and small molecules said Researchers at the University of Wisconsin-Madison School of Pharmacy.

"We're finding this enzyme glycosylates all sorts of molecules," Nature magazine quoted Jon Thorson, professor of pharmaceutical sciences, as saying while describing the process of adding natural sugar molecules to other chemical molecules to enhance their biological effects.

Thorson likens the newly evolved enzyme, which he developed working with colleagues Gavin J. Williams and Changsheng Zhang, to a “Swiss Army enzyme”, a catalyst that can decorate many different chemical molecules with all sorts of sugars to alter their biological effects.

Enzymes are proteins that act as catalysts across biology, from single-celled organisms to humans. They are also important for making so-called natural drugs, therapeutic agents based on the blueprints of chemicals produced in nature by plants and microorganisms.

Such natural sugar-bearing chemicals are the basis for some of medicine's most potent antibiotics and anticancer drugs, as exemplified by the antibiotic erythromycin and the anticancer drug doxorubicin.

Although scientists can sometimes manipulate how sugars are added or subtracted to a chemical molecule to alter its therapeutic properties, it is difficult and not always possible to routinely modify them to enhance their beneficial effects.

Advertisements

The scientists created the new enzyme by generating random mutations in genes that make a naturally occurring enzyme. They put the altered genes into a bacterium that fabricated a series of randomly mutated new enzymes, which were then tested in a high throughput screen where chemical molecules engineered to fluoresce stopped glowing when a sugar was successfully attached.

"We're transferring the sugar to a beacon. When you attach a sugar, you shut off the fluorescence," Thorson said.

Advertisements

He said that the development of the screen was critical as it overcame a key limitation in the glycosyltransferase field.

"We're assaying hundreds of very interesting drug-like molecules now with newly evolved glycosyltransferases. The ability to rapidly evolve these enzymes has opened a lot of doors," he said.

Thorson says that the new technology may help generate a range of potential therapeutic agents, including important anti-inflammatory and anti-cancer compounds and antibiotics.

He believes that the new finding may led to the creation of a "super bug", an engineered bacterium that can perform the entire process in a laboratory dish.

"There's no doubt that this is going to work in vivo. We can create a bug where you feed it sugars and the compounds you want to hang those sugars on" to arrive at new medicines," Thorson said.

Source-ANI
JAY/J