Pharmaceutical companies that need to test how well drug candidates inhibit glycogen synthase can now purchase technology developed at the Indiana University School of Medicine that produces the difficult-to-make enzyme in larger quantities, more quickly and in a purer form than traditional methods were able to achieve.
Thomas Hurley, Chancellor’s Professor and interim chair of the Department of Biochemistry and Molecular Biology, developed the technology. Wisconsin-based BellBrook Labs Inc. has licensed it through the Indiana University Research and Technology Corp. Robert Lowery, president and CEO of BellBrook Labs, said the company is commercializing it for use with the company’s proprietary Transcreener HTS Assays.
“Drug discovery scientists can use Transcreener HTS Assays to measure the activity of glycogen synthase in samples treated with drug candidates, which could lead to more-effective drugs for rare disorders,” Lowery said. “One of those disorders is Pompe disease, which is caused by the accumulation of glycogen to toxic levels. The primary effects range from walking problems to the inability to breathe. The standard treatment is costly and complicated, which is leading researchers to investigate using a small molecule to inhibit glycogen synthase and slow down the production of glycogen.”
Lowery said scientists need highly purified, active glycogen synthase to find drug molecules that inhibit it.
“It is difficult to make the enzyme for tests using traditional methods because it must be co-expressed with an accessory protein called glycogenin,” Lowery said. “This requires a specialized dual expression vector and an atypical expression protocol.”
Hurley and his colleagues developed a new approach to production.
“It uses a multi-component expression vector that allowed us to produce human glycogen synthase simultaneously with glycogenin,” Hurley said. “We believe the complex formed between these two enzymes is what enables the system to produce active and soluble human glycogen synthase.”
Hurley’s research to develop the technology and optimize the production protocol was supported with funding from the National Institutes of Health. It was published in the peer-reviewed journal Protein Expression and Purification.