| Popis: |
Heparin is a highly sulfated form of the polysaccharide heparan sulfate and is commonly used as an anticoagulant. As an animal sourced product, heparin is a heterogeneous product, containing polysaccharides that differ in length and sulfation pattems. After contamination of heparin with over-sulfated chondroitin sulfate in 2007, and in the interest of studying other potential pharmacological activities, there have been efforts to synthesize heparin in a cost-effective manner. Specifically, chemoenzymatic synthesis is a leading method for efficient and inexpensive production of heparin. One of the limitations in this process is the cost of purchasing the two starting sugarnucleotides. Previously, our lab has developed methods to produce UDP-GlcNTF A (uridine diphosphate N-trifluoroacetylglucosamine) effectively, but there is still considerable expense in purchasing UDP-GlcA (uridine diphosphate-glucuronic acid). Using previous reports of sugar-nucleotide chemoenzymatic synthesis on a large scale, the purpose of my research has been to develop and implement a method to enzymatically synthesize UDP-GlcA, an expensive starting reactant, from glucose, a more cost-effective starting material. Note that this is an extensive project and includes additional work for my graduate program. Therefore, this report reflects only a portion of my research, focusing in particular on some problem solving aspects of research that have been overcome during my time in the honors program. |
