Canadian chemists unravel biological challenge

TORONTO—A chemistry professor and graduate student at the University of Toronto have teamed up for research that may not only allow scientists to generate new kinds of proteins, but could also eventually lead to practical applications such as simplifying drug development.

Professor Ronald Kluger and doctoral candidate Svetlana Tzvetkova led a team that modified the steps involved in creating proteins.

In a statement, Kluger says he became interested in the possibility of manipulating proteins after learning about efforts to produce "designer amino acids."

"I was intrigued by the possibility that someone could actually attempt to make proteins with amino acids that aren't specified in the genetic code at all," says Kluger.

In nature, there are 20 different amino acids that can link together to make proteins. Protein creation begins with DNA, which sends out genetic instructions via an RNA message (mRNA) to the ribosomes in human cells. tRNA collect the amino acids and bring them to the ribosomes. The tRNA then aligns with mRNA so the amino acids can join to form proteins. The catch is that an amino acid has to be activated by a specific enzyme before the tRNA can scoop it up.

Kluger and another student, Lisa Cameron, found that they could mimic the critical action of this enzyme when they combined common inorganic chemicals called lanthanum salts with a chemically activated amino acid. Tzvetkova showed the chemical mimic will allow an amino acid to attach to the complex tRNA molecule in just the right place.

The results of the research were e-published in the Dec. 4 issue of the Journal of the American Chemical Society. The research could be developed to allow tRNA to collect new "unnatural" amino acids, which Kluger points out could "give anyone the ability to create totally new materials that have nothing to do with the genetically defined functions of proteins."

According to Kluger, scientists have been trying this type of modification for years, using methods involving a number of difficult steps.

"They started to mutate the enzymes instead of doing a chemical alteration," says Kluger, who explains the elegance of his method is that it changes how amino acids are added to tRNA "in one step, just the way nature does it."