Researchers find novel method to modify drugs

The new finding has the potential to alter the beneficial properties of compounds to create variants that can be screened for their therapeutic value. In addition, the scientists claim that the technology required to create the new compounds is simple and scalable making it more attractive to the pharmaceutical industry. The need for new antibiotics to combat bacteria that have become resistant to existing drugs is an increasingly desperate one. The new vancomycin variants, for example, may become important in the battle against drug-resistant staph infections. According to a new study published last month in the New England Journal of Medicine 59 per cent of skin and soft tissue infections in emergency rooms nationwide were resistant to antibiotics now in use. The new process involves manipulating a family of enzymes nature uses to position the sugar molecules of a drug and confer a specified biological effect. The technique has already yielded more than 70 variants of calicheamicin, an anti-tumour drug, and novel analogs of vancomycin, an antibiotic used to fight drug-resistant bacterial infections. The study found that the enzymes are capable of modifying natural products in a much more flexible way than previously thought. The key new finding is the catalytic activity of the enzymes can be reversed to take a sugar molecule from one natural product and confer it on another in a single reaction. "The work opens the door to a variety of new opportunities in the natural product drug arena,"​ said Jon Thorson, a professor of pharmaceutical sciences at the University of Wisconsin-Madison "There are a number of antibiotics and anticancer agents this can be applied to."​ In nature, plants and organisms can make chemicals that can be used as primary sources of drugs employed to fight cancer and thwart infection. Key chemical features of such drugs are natural sugars, molecules that frequently dictate a chemical compound's biological effects. For years, medicinal chemists have modified those natural agents to develop variants that have new or more potent disease-fighting properties. However, scientists have found it difficult to easily and routinely modify the sugar molecules that make such agents medicinally useful. "This discovery provides a reaction that eliminates the need to synthesise exotic sugar donors,"​ Thorson said. The team's discovery, Thorson adds, may have implications beyond the ability to soup up natural drugs because similar sugar-transferring enzymes play many other roles in biology. "In one vessel, the enzyme can be used to do all of the chemical heavy lifting, synthesising the new compounds according to how the enzyme is manipulated,"​ Thorson added.