Sugar Polymer Engineering with Glycosaminoglycan Synthase Enzymes: 5 to 5,000 Sugars and a Dozen Flavors

摘要

Glycosaminoglycans [GAGs] are used currently as therapeutics, but the controlled manipulation and/or synthesis of these sugars has been difficult or impossible in the past. A variety of GAG polysaccharides and oligosaccharides may now be synthesized in vitro with the advent of recombinant Pasteurella multocida synthases. Narrow size distribution polymers ranging from 5 to 1,500 kDa are produced with synchronized, stoichiometrically-controlled reactions. Alternatively, monodisperse oligosaccharides ranging in size from 5 to 22 monosaccharides are synthesized in a step-wise fashion with immobilized enzyme reactors. Either pure or chimeric sugar chains are possible in both types of synthetic schemes. Overall, these strategies should allow the production of a wide variety of novel polymers with potential utility in the treatment of cancer, wound-healing, thrombosis, immune dysfunction, or inflammation.