Artemisinin from the plant Artemisia annua is the most potent pharmaceutical for the treatment of malaria. In the plant, the sesquiterpene cyclase amorphadiene synthase, a cytochrome-dependent CYP450, and an aldehyde reductase convert farnesyl diphosphate (FDP) into dihydroartemisinic aldehyde (DHAAl), which is a key intermediate in the biosynthesis of artemisinin and a semisynthetic precursor ...

Herein, we describe an efficient and high-yielding method to synthesize hyaluronan oligosaccharide-lipid conjugates. This strategy is based on first covalently attaching diphytanoyl glycerophosphatidylethanolamine (DiPhPE) to commercially available high molecular weight hyaluronic acid (HA), via the carboxylate group of the glucuronic acid using carbodiimide chemistry. The HA-lipid conjugate mi...

A biotinylated heparosan hexasaccharide was synthesized using a one-pot multi-enzyme strategy, in situ activation and transfer of N-trifluoroacetylglucosamine (GlcNTFA) to a heparin backbone significantly improved the synthetic efficiency. The biotinylated hexasaccharide could serve as a flexible core to diversify its conversion into heparan sulfate isoforms with potential biological applicatio...

.................................................................................................. v List of publications ................................................................................... vii Table of contents ...................................................................................... ix Abbreviations ....................................................................

Glycoproteins with chemically defined glycosylation sites and structures are important biopharmaceutical targets and critical tools for glycobiology. One approach toward constructing such molecules involves chemical glycosylation of aldehyde-tagged proteins. Here, we report the installation of a genetically encoded aldehyde tag at the internal glycosylation site of the crystallizable fragment (...

Heparin is an anionic polysaccharide that is widely used as a clinical anticoagulant. This glycosaminoglycan is prepared from animal tissues in metric ton quantities. Animal-sourced heparin is also widely used in the preparation of low molecular weight heparins that are gaining in popularity as a result of their improved pharmacological properties. The recent contamination of pharmaceutical hep...

Sialyl Lewis x (sLe(x)) derivatives conjugated to readily visualized molecular labels are useful chemical probes to study selectin-carbohydrate interactions. Localization of the selectins on the surface of leukocytes and activated endothelial cells can be detected through fluorescence of bound selectin ligands. Herein we present a short chemoenzymatic synthesis of a fluorescently labeled bivale...

The purification of heparin from offal is an old industrial process for which commercial recipes date back to 1922. Although chemical, chemoenzymatic, and biotechnological alternatives for this production method have been published in the academic literature, animal-tissue is still the sole source for commercial heparin production in industry. Heparin purification methods are closely guarded in...

O-Sulfated sialyl Lewis x antigens play important roles in nature. However, due to their structural complexity, they are not readily accessible by either chemical or enzymatic synthetic processes. Taking advantage of a bacterial sialyltransferase mutant that can catalyze the transfer of different sialic acid forms from the corresponding sugar nucleotide donors to Lewis x antigens which are fuco...