| Volume 4, | Number 1 | March/April 1996 |
The Protein Crystallization Facility (PCF), designed and developed by the Center for Macromolecular Crystallography (CMC), has produced space experiment results that may lead to a better way to administer insulin to diabetics. These experiments have enabled Eli Lilly, a commercial partner of the CMC, to acquire detailed information about the structure of human insulin, which could facilitate the development of a second-generation insulin formulation.
The design of the original PCF hardware came about in 1990 as the CMC worked closely with another commercial partner, ScheringPlough, on the crystallization of alpha interferon. This protein pharmaceutical is used for treating more than 14 diseases, including hairy cell leukemia, multiple myeloma, venereal warts, AIDS-related Kaposi's sarcoma and chronic hepatitis B and C. The PCF hardware subsequently proved effective in producing batches of crystals of other significant proteins, such as insulin. These crystals are critical to structure-based drug design, a relatively new technology, which conceives new medicines based on a knowledge of the structure of macromolecules (typically proteins) involved in diseases.
The PCF experiments in microgravity have proven significant because they have produced useful protein crystals for obtaining x-ray diffraction data. These data allow the techniques of protein crystallography to deduce the detailed structure of proteins. This, in turn, helps design new drug compounds that effectively target disease processes and cause fewer undesirable side effects. The PCF has produced crystals in microgravity that are significantly larger, with higher internal order than their Earth-grown counterparts.
The PCF results also indicate that the facility could be applied to the production of protein pharmaceutical formulations used as crystalline suspensions in time-released medications. The crystalline populations typically produced by the PCF in microgravity are more homogeneous in size than Earth-grown crystals. This characteristic is vital for the predictable release and dosing of crystalline therapeutics. The results from the alpha interferon experiments suggest that the use of PCF-type hardware may be a useful starting point for producing crystalline time-release protein pharmaceuticals.
The PCF induces crystallization by temperature change. The PCF hardware contains vials that vary in volume from 1 to 1,000 milliliters. These vessels are held in a structure that provides additional sample containment and thermal insulation. This assembly is accommodated within an enclosure that provides a controlled and programmable thermal environment. The assembly provides a thermal path from the enclosure through each vial. The overall design provides the thermal gradient desired for each protein to be processed. The hardware easily adapts to varying experiment requirements and can include laser light-scattering instrumentation to detect the onset of crystal nucleation, allowing for the interactive control of the thermal gradient.
The PCF is available to the CMC's commercial partners for Earth and on-orbit crystallization experiments to provide information critical to novel drug discovery and development. In summary, PCF microgravity crystallization experiments can provide:
The PCF system is one major element of the spaceflight hardware systems of the CMC. These systems support the combined efforts of the NASA commercial development of space program, the CMC, and the CMC's pharmaceutical partners to efficiently bring to market new, effective pharmaceuticals to help people lead healthier, happier lives. The CMC is one of eleven NASA Centers for the Commercial Development of Space.
For more information about the PCF, contact Larry DeLucas at the CMC Phone: 205/934-5329 E-Mail: DeLucas@orion.cmc.uab.edu Or contact Marianna Long at the CMC Phone: 205/934-8991 E-Mail: Long@orion.cmc.uab.edu Please mention that you read about it in Innovation.