|Ph.D Student||Solomon Dmitry|
|Subject||Towards Carbohydrate-Based Catalytic Systems: Design,|
Synthesis and Evaluation of the First Catalytic
|Department||Department of Chemistry||Supervisor||Professor Timor Baasov|
Many thousands of chemical reactions proceed simultaneously in our bodies, involving often-rare reactants in dilute solutions at comparatively low physiological temperatures. Left to themselves, most such reactions would creep along at unacceptably slow rates, if at all. Fortunately, the body produces a wide variety of catalysts, substances that dramatically facilitate and increase the rate of specific chemical reactions. Most are enzymes, proteins coded by genes and named after the substrate they transform (for example DNAse help cleave DNA molecules). In comparison to such flashy proteins, the polysaccharides, long strings of linked sugars such as starch and cellulose, seem staid and anti-social.
Our research reversed this longstanding prejudice by showing that polysaccharides can also function as catalysts, and biologically important ones at that. For this purpose we utilized two naturally occurring sugar-based “building blocks”, GlcN (2-amino-2-deoxyglucose) and Kdo (2-keto-3-deoxy-octulosonate). Linking two Kdo molecules and then three GlcN molecules together gave two fragments which were combined to form 5-sugar (pentasaccharide) in 32 chemical steps with overall yield of 2.2%. Upon testing this pentasaccharide was found to have a broad spectrum of biologically important catalytic activities. For example, it facilitated the cleavage of DNA, the genetic material, and cleavage of GTP, chemical important in energy storage, usage and metabolism. The rate of hydrolysis of GTP to GDP was, in fact, increased 500 times.
This pioneering research demonstrated for the first time the catalytic power of a small, synthetic oligosaccharide. This “primordial glycozyme” has many unique features that combine the simple with the complex, supplying further challenges for intensive investigation. We believe that such efforts should lead to a new era in our understanding of biocatalysis and catalysis required for design.