The 2nd International Conference on Drug Discovery & Therapy: Dubai, February 1 - 4, 2010


Invited Speaker

An Enzymatic Approach for Preparing Synthetic Heparin
Jian Liu
USA

Heparan sulfate (HS) represents a substantial portion of glycans that perform essential physiological functions. Heparin, a special form of HS, is a commonly used anticoagulant drug. Heparin is currently isolated from pig intestine. A contaminant was recently discovered in US, Europe, Asia and Australia. The contaminated heparin led to close 100 deaths and nine hundred cases of strong adverse reactions. Thus, a method for preparing synthetic heparin in a confined facility is highly desirable. Chemical synthesis of HS oligosaccharides that are larger than hexasaccharides is extremely difficult. We have developed an enzyme-based approach to synthesize heparin and heparan sulfate. Total of five enzymatic steps are involved in the synthesis, and we have expressed all of the enzymes in bacteria at high yields. A low cost sulfo donor system was also successfully coupled with the synthesis, which reduced the cost of the synthesis by more than 1000-fold. Our method has demonstrated the feasibilities of the synthesis of the heparan sulfate with different biological functions in multi-milligram scales. We hope that our method could not only make sufficient amount to replace the heparin from animal sources but also permit us to design the structure of heparin to eliminate the side effects.












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