ISTN has developed a silica-chitosan based nanopore material to which it can effectively immobilize enzymes. The basic concept of NEED is to immobilize enzymes onto a nanopore support and to enhance its performance by engineering the support’s surface composition as well as pore morphology. Once the enzymes are immobilized it is possible to utilize the numerous interfaces existing between an interpenetrating network of hydrophobic silica gel and hydrophilic chitosan polymer to modulate and enhance the enzyme’s activity and selectivity. Initial studies have shown this technology’s potential to be used to produce a number of valuable compounds including chiral drug intermediates, fine chemicals, food/beverage compounds.

Clinical studies have clearly demonstrated the superior value of chiral drugs. An overwhelming majority of clinical results have shown that only one enantiomer would provide the desired activity while the counterpart being either inactive or, even toxic. Among the current top ten selling drugs (such as Lipitor, Zocor, etc.), nine active ingredients are chiral. At present, over half of the chiral products were made by traditional method (pool and separation), one third was achieved by chemocatalysis, and only about 15% were derived from biocatalysis. However, the trend is changing in favor of biocatalysis due to the tremendous progresses in biomedicines, including the high throughput screening, modern molecular biology techniques such as directed evolution as well as surges in the fields of genomics and bioinformatics. With these skills, scientists can further improve an enzyme by applying protein engineering and evolution design.

The rapid development in material nanotechnology is likely to favor this trend shift towards enzyme catalysis as well. Gradually, scientists are able to accomplish what was once dreamed; understanding properties, controlling processing, and engineering structures at the nanometer scale. Thus, new nanopore materials can be designed for enzymes to accomplish both immobilization and performance enhancement simultaneously (NEEDä). For enzymes attached onto a nanopore substrate, their chemical environment could be favorably modified by their nearby surface ligands due to the close distances (few nanometers) among functional groups.

NEEDä - COMMERCIAL POTENTIAL

As mentioned earlier, most drugs often require one pure chiral structure. A mixture of enantiomers would require FDA’s approval of two drugs, not just one. Being able to manufacture and separate the effective enantiomer simultaneously will provide a great benefit to pharmaceutical suppliers. The recent advances in food and nutrition sciences have also demonstrated the importance of composition and structure precisions in fats (for examples, the danger of cis to trans isomerization during chemical hydrogenation of vegetable oils, and the benefits of ω3-unsaturated fatty acids). Another significant business opportunity for optically active compounds is in the $45 billon Liquid Crystal Display (LCD) industry. This industry will become the biggest market for fine chemicals in the coming decade as sales increase and as the manufacturing processes become more complex. Enzymatic production of fine chemicals for the pharmaceutical, food/nutrition, LCD industries, in replacement of traditional production using sophisticated synthesis and separation schemes, could also create substantial commercial benefits due to the speed and simplicity of this production method.

NEEDä - CURRENT STATUS

ISTN has recently received a $173,000 Phase-II SBIR grant from the NIH to continue development of its NEEDä technology. This grant will allow the technology to begin to target several of its intended application areas. ISTN is seeking partners in developing this technology for commercial use.

Inquiries regarding this technology, please contact:

Allan David
Biomedical Technology Manager
aedavid@istninc.com