Purifying proteins

The process of multimodal chromatography has generated interest from the pharmaceutical industry for use in the purification of drug components. A study of the protein absorption and binding regions has provided fresh insight into how this technique works, and could lead to better processes and cheaper drugs.¹

Multimodal chromatography separates proteins from their surrounding materials by attaching them to ligands. The more selective the ligand is at binding to a specific protein, the more efficient the process is, and the less additional steps are required to produce the final drug. This results in reduced costs for the production of the drug.

To understand what makes a ligand successful the team compared modified proteins using multimodal chromatography and ion exchange chromatography. No difference was seen in the binding using ion exchange but huge fluctuations were reported in the binding of the different mutations within the multimodal system. To further understand why this was happening the team used NMR. This allowed them to determine what part and type of protein the ligands were binding to and how strongly they would bind. The results validated the comparison experiments, showing that each of the protein mutants that strongly fluctuated in their binding strength in the multimodal chromatographic system were also the same ones identified with the NMR.

1. W.K. Chung et al., PNAS, 107(39), 16811–16816 (2010).

This story originally appeared in The Column. Click here to view that issue.