The Commerce Department’s National Institute of Standards and Technology has announced that it will renew a multiyear research award under the Advanced Technology Program to 3-Dimensional Pharmaceuticals Inc. (Exton, Pa.) to develop a combination of novel protein engineering and crystallization methods to acquire previously unavailable molecular structure data on an important class of proteins belived to play a role in cardiovascular disease, pain, schizophrenia and many other medical problems.
The NIST award renewal is for $496,069. The three-year project, begun in 1995, is projected to receive a total of approximately $1,998,000 in ATP funding, matched by approximately $1,671,000 in industry funding.
Advanced Technology Program awards are designed to help industry pursue risky, challenging technologies that have the potential for a big pay-off for the nation’s economy. ATP projects focus on enabling technologies that will create opportunities for new, world-class products, services and industrial processes, benefiting not just the ATP participants but other companies and industries--and ultimately consumers and taxpayers. The ATP’s cost-shared funding enables industry to pursue promising technologies that otherwise would be ignored or developed too slowly to compete in rapidly changing world markets.
Detailed information on this project, Crystallization and Structural Determination of G-Coupled Protein Receptors, is provided below.
Many therapeutic agents work by modifying, interfering with, or inactivating cellular proteins. Among the top 25 pharmaceuticals, one-third act on proteins embedded in cell membranes. These proteins include the molecular receptors through which cells interact with and respond to extracellular effectors. These receptors play central roles in cardiovascular disease, pain, schizophrenia, and many other pathologic processes. This same class of proteins is exceedingly difficult to isolate in quantity, and attempts to crystallize these proteins have been unsuccessful. This is a problem, because drug discovery efforts increasingly depend upon detailed knowledge of the molecular structure of proteins provided by X-ray crystallography. 3-Dimensional Pharmaceuticals, Inc., proposes to solve this dilemma for an important group of membrane proteins, called G-protein coupled receptors (GPCRs), by using novel expression and purification systems to obtain larger amounts of the proteins. Promoting crystallization of the resulting protein molecules will require novel genetic engineering techniques to enhance the tendency of the receptors to pack into crystals. If successful, previously unavailable structural data on GPCRs could lead to new drugs for many applications, among them treatments for cancers, autoimmune diseases, cardiovascular and metabolic disorders, schizophrenia, and pain.
3-Dimensional Pharmaceuticals, Inc.
Technologies: Human Therapeutics
Project length: 3 years
ATP funds: $1,998 K
Cost-shared funds (est.): $1,671 K
Total project funds (est.): $3,669 K
Contact: Dr. F. Ray Salemme, (610) 458-6040, salemme [at] 3dp.com (salemme[at]3dp[dot]com)