Rice University scientists have created a way to fine tune a process critical to the pharmaceutical industry that could save a lot of time and money.
A combination of the Rice technique that provides pinpoint locations for single proteins and a theory that describes those proteins’ interactions with other molecules could widen a bottleneck in the manufacture of drugs by making the process of isolating proteins five times more efficient.
The work by Rice chemist Christy Landes and her team will be reported online this week in the Proceedings of the National Academy of Sciences.
A critical step in drug manufacture is the separation of “proteins of interest” — the active elements in drugs — from other materials. The primary method used is ion-exchange chromatography, which is like using a colander to separate cooked pasta from water. In this case, a separation column removes proteins from water and other cellular material. Landes said raw material containing the proteins is injected into the top of a separation column, or tube. The mixture is the “mobile phase” of the process, and it can either be pulled through the tube via gravity or pushed through.
Along the way, the liquid encounters a “stationary phase,” a structure that incorporates ligands — binding ions or molecules. In theory, they capture only the proteins of interest, while the unwanted material passes through. The proteins are later washed off in a purifying step called elution. It’s this stationary phase that Landes said should be tuned. That can only happen by knowing what occurs at the molecular level.
“Our fundamental understanding of this process at the level where proteins bind to ligands, which basically drives several different industries, is ridiculously small,” she said. “We should take care to understand everything about separation, because up to half the cost of bringing a drug to market is for separation and purification — and the global pharmaceutical market is more than $100 billion annually. Do the math!”
The remarkable part, Landes said, is that the stochastic theory of chromatography, which describes single-molecule interactions and could improve the process, has been around for decades. But until now, nobody has had access to a tool to validate it through experimentation, especially for single proteins.
“It can actually describe and let us tune at the chemical level what’s really going on in separations,” she said of the theory. “But the only way to use the theory is to collect the information that describes the interaction one protein at a time.”