Martek Biosciences Corp. signed its first collaborative agreement witha commercial drug developer involving its proprietary enablingtechnology, Celtone M, which determines the three-dimensionalstructure of human proteins using nuclear magnetic resonance (NMR).The agreement, with Genetics Institute, involves an undisclosed up-front payment to Martek and royalties _ on a sliding scale dependingon the importance of Celtone M in development of final products _ ofless than 10 percent, Larry Horn, Martek's director of businessdevelopment, told BioWorld.Genetics Institute, of Cambridge, Mass., will target sets of humanproteins for the larger disease markets, said Horn, who added that theagreement is non-exclusive with respect to disease targets.Celtone M is a medium that allows mammalian cells to grow andincorporate the stable isotopes, which the Columbia, Md. companyproduces using its microalgae."Being able to utilize this technology significantly enhances theopportunities we have to pursue structure-based drug design," saidDale Cumming, director of structural biology at Genetics Institute."Now we can access a set of molecules for NMR structure analysis thatwere previously unattainable. There are a number of potential targetmolecules whose functional activity requires biosynthesis inmammalian cells."While a number of companies determine the three-dimensionalstructures of proteins using X-ray crystallography, the method islimited to human proteins that crystallize.Jonathan Miles Brown, Martek's director of technical marketing andinventor of the technology, told BioWorld, "The real role for NMR isto look at those proteins that don't crystallize."Martek's expertise lies in the replacement of carbon and nitrogen atomsin biomolecules with carbon 13 and nitrogen 15, respectively.Celtone M, Brown said, is a mixture of all the amino acids themammalian cells require, all of them universally labeled, mixed withlabeled carbohydrates and, where necessary, labeled fatty acids."This means proteins such as receptors can be expressed in labeledform and, for the first time, consequently, can have their three-dimensional structure determined by NMR. That means the techniquesof structure-based drug design will be used against receptors."Last year Martek and Columbia University entered into an agreementwhereby the New York university would use Celtone M to determinethe structure of human chorionic gonadotropin (hCG), a protein thatcontrols fertility. Columbia and Martek would share royalties resultingfrom that research, Horn said.Horn said Martek expects further collaborative arrangements involvingCeltone M, for which a patent application has been filed.

-- Jim Shrine

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