Searching for New Reactivity: Merging Enzymatic Catalysis with Iron Catalysis for Highly Stereoselective Glycosaminoglycan Assembly

Complex glycans are directly involved in essential life processes, but it is challenging to precisely assemble them in sufficient quantities with high homogeneity. One major hurdle is that the stereoselectivity in glycosylation often varies with substrates, thus it is difficult to develop an exquisitely selective glycosylation method that is also broadly effective. In particular, searching for a general solution for stereoselective assembly of 1,2-cis-glycosidic bonds is an unsolved challenge. The lecture will focus on the discovery of a mechanistically unique and generally applicable approach for exclusively 1,2-cis-selective glycosylation. In this lecture, we will also discuss a generally applicable glycosaminoglycan (GAG) assembly strategy by merging the catalytic power of sulfotransferases (SULTs) with two distinct iron-catalyzed glycosylation reactions that have been recently discovered in our lab. Every glycosidic linkage in heparan sulfate (HS) was assembled by one of these iron-catalyzed, entirely stereoselective glycosylation reactions. An array of sulfate groups that are essential to the functions of HS were installed at their desired locations via the SULT-controlled sulfation reactions.

Speaker: Hao Xu, Brandeis University