Conventional SPR Shake-Up
Graffinity’s screening method literally turns conventional SPR methodologies upside down. Rather than immobilizing the target protein on the chip and running each compound in the library over it, it immobilizes each compound in its own sensor field and runs the target protein over them, explains Mathias Woker, CBO, who adds that this method has a number of advantages.
First, he says, it can vary the point at which the compound binds to the chip, presenting different surfaces to the target protein.
Renate Sekul, Ph.D., head of research and development at Graffinity, thinks that “it is highly important to screen an active protein,” which is feasible in this system since the protein is in solution. This also makes standardizing the binding conditions across the library much easier.
Second, it is fast, Woker notes, making it well suited to high-throughput screens. This is partially because chip regeneration is not as much of an issue, and partially because they measure light spectrum shifts rather than light angle shifts to minimize errors, Dr. Sekul said.
Woker claims that “a Graffinity screen of 110,000 compounds takes 10 days where usually an experiment would take more than three months with strong limitations concerning the solubility of the compounds screened and the conformity of the results concerning consistent protein quality over the experiment time frame.”
Since 2002, Graffinity has screened over 80 targets, including kinases, phospodiesterases, proteases, nuclear hormone receptors, and even RNAs, and found hits for all of them, Woker concludes.