Glyco@Seminar: Paul DeAngelis

on the May 27, 2019

May 27th, 11:00am
Paul DeAngelis from University of Oklahoma Health Sciences Center (USA) will give a talk about “Glycosaminoglycan Engineering: Designing Natural Sugar-based Therapeutics & Drug Delivery Systems”.
Abstract
Glycosaminoglycans (GAGs) are essential polymers in all vertebrates and have many medical applications ranging from anticoagulants to biomaterials. These linear polysaccharides are composed of repeating [GlcUA-HexNAc] disaccharide subunits. The pathogenic microbe Pasteurella multocida produces extracellular capsules composed of GAGs (hyaluronan, chondroitin, and heparosan depending on the strain serotype) to defeat host defenses via molecular camouflage. We have harnessed several bacterial GAG synthases, the bifunctional enzymes that polymerize the GAG chains using UDP-sugar precursors, for chemoenzymatic synthesis in vitro to make novel GAGs with potential for a variety of medical applications. Our biotechnology focus is on drug delivery, therapeutic, and biomaterial platforms.

Sugar polymers, especially molecules with chain lengths longer than five monosaccharides, are difficult to produce by strictly organic synthesis in a defined form as well as usually generate ~1,000:1 waste to target molecules. 'Green' chemoenzymatic synthesis offers the potential to harness enzyme catalysts for rapid, efficient reactions. We previously developed methods to construct GAG polysaccharides of any desired size from 10 to 25,000 kDa in synchronized reactions as well as make short GAG oligosaccharides (0.8 to 5 kDa) in step-wise addition reactions. We have enhanced the GAG synthetic repertoire by employing novel UDP-sugar derivatives that allow further functionalization of the polymers.

Overall, GAG polymers can be customized for medical use in different applications by varying the synthase enzyme and the UDP-sugar analogs employed as well as altering the sugar addition strategy.




Published on May 17, 2019

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