Understanding chromatography saves pharma big money
By fine tuning a critical process in drug manufacture, researchers at Rice University say they can widen a bottleneck and save the pharmaceutical industry time and money.
The new technique can pinpoint locations for single proteins and, in combination with a theory describing how these proteins interact with other molecules, could isolate proteins five times faster than is currently possible.
Their method used ion-exchange chromatography where the stationary phase is a mixture of ligands, which in theory capture only the proteins of interest. This stationary phase could be fine-tuned, but only if researchers understand what happens at the molecular level, said Christy Landes, who led the study.
“Our fundamental understanding of this process at the level where proteins bind to ligands, which basically drives several different industries, is ridiculously small,” Landes 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 maths!”
Landes said that the remarkable part is that the stochastic theory of chromatography which could improve the process has been around for decades, but until now no-one had access to the tools to validate it through experimentation.
“It can actually describe and let us tune at the chemical level what’s really going on in separations,” she said. “But the only way to use the theory is to collect the information that describes the interactions one protein at a time.”
Landes and her team found super-resolution technique mbPAINT - developed to identify individual sequences along DNA - worked just as well for the capture and release of proteins and ligands in chromatography.
Researchers could then resolve structures as small as 30nm by building up pictures over time of a probe molecule which fluoresced when temporarily captured by immobilised DNA. This will give researchers a more precise look at the mechanism making column chromatography possible.
The results showed that at the molecular level, ligands embedded in the stationary film - an agarose gel - would only capture proteins, synthetic peptides, when at least three ligands were clustered together. Landes said this knowledge will enable stationary phases in chromatography to be better engineered and optimised.
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