Bulk Protein Crystallization — Principles and Methods

Crystallization is a powerful method of purifying proteins. For many decades, industry has used crystallization to purify insulin for treatment of diabetes, and proteases for use in laundry detergent. However, central focus has been on crystallization for the production of diffraction-quality single crystals for protein structure determination by crystallography. The demands on crystals are quite different for structure determination vs. purification duringSHUKLA: "dk3347_c005" — 2006/5/23 — 17:55 — page 160 — #2played a cameo in the epic of protein crystallography research. Yet, much can be learned from protein crystallography and applied to bulk protein crystallization. High throughput screening techniques, statistical design-of-experiments approaches, and thermodynamic theories for protein solubility, all developed for protein crystallography research are also beneficial to the development of bulk protein crystallization processes. The time has come for rapid growth in the use of bulk crystallization for proteins. Purification is only one method of implementation. Formulation is another. In formulation, the increased stability, higher concentration doses, controlled release dosages, and potential for administration of doses by subcutaneous injection rather than intravenous infusion are all driving increased interest in bulk protein crystallization.