An aging population, increasing prevalence of chronic diseases, drug resistant pathogens, and many other clinical challenges have escalated demand for effective and safe pharmaceuticals. Natural products are a time honored source of prescription pharmaceuticals, as reflected in the fact that as much as 75% of the modern pharmacopeia is from natural products or derivatives.

DENALI is the only biotechnology Company dedicated to prospecting natural products for pharmaceutical discovery in the Arctic and boreal biomes. Distinct from tropical and temperate species, the flora and fauna of this region produce novel molecules in response to harsh environmental conditions and extreme stress. The biochemistry of psychrophilic organisms is fascinating, in that:

Structurally, psychrophilic enzymes possess

• More polar, less hydrophobic residues
• Additional glycine and low arginine/lysine ratio
• Fewer hydrogen bonds, aromatic interactions and ion pairs
• Lack of salt bridges
• Additional surface loops with increased polar residues and/or decreased proline content
• Modified alpha-helix dipole interactions
• Reduced hydrophobic interactions between subunits


Catalytically, enzymes of psychrophiles demonstrate

• Decreased temperature and pH stability
• More catalytic efficiency, less thermodependence
• Broader substrate specificity
• Higher kcat value, lower km, or combination

This unique enzymatic profile offers unprecedented opportunity for discovery of unforeseen molecules for pharmaceutical applications.

Over the past decade, the DENALI team has collected more than 10,000 specimens with psychrophilic and other extremophilic characteristics. The Company is amassing a large and structurally diverse compound library from plants, microorganisms, and aquatic/marine organisms for new pharmaceutical discovery. Source materials are selected through ethnopharmacologic traditions of Alaska Natives, chemotaxonomic similarity to known drug-producing source organisms of other origins, or chemical ecology where organisms are producing bioactive molecules in a symbiotic or competitive relationship.

DENALI's core technology is focused primarily on adding value to naturally occurring compounds through efficient specimen extraction, and chemical purification, characterization, and modification techniques. The Company has developed a high-throughput process capable of selectively extracting those compounds with "drug-like" properties from source materials. Hundreds of extracts of uniquely high-quality composition that contain up to thousands of bioactive compounds ready for drug discovery screening without further purification can be generated within a day.

To rapidly expand the size, diversity, and proprietary value of the library,DENALI is devising combinatorial chemistry methods to modify naturally-occurring pharmacophores. DENALIhas also engineered a non-mammalian model system for pharmaceutical discovery based on the common baker's yeast, Saccharomyces cerevisiae, to evaluate simultaneously anti-diabetic, anticancer, and anti-infective properties of its compound library. As a genetically manipulable model for human disease, yeast is adaptable to high-throughput screening assays for numerous therapeutic categories.