SCIENCE & TECHNOLOGY
AUTOMATED GLYCAN SYNTHESIS
N ICOLA POHL
amounts of sugar monomers have to be used to drive the solid-phase reactions to completion. Some of these building blocks are wasted, and this can be quite costly because carbohydrate monomers are expensive. On the other hand, the solid-phase particles make it easy to isolate and purify ACS MEETING NEWS: Advances could make the oligosaccharide products. oligosaccharides more accessible for study Pohl’s group is developing a synthesizer that carries out linkage reactions in solution and thus eliminates the need for large OLIGOSACCHARIDES continue to defy drate synthesis but weren’t compatible with excesses of sugar building blocks. And it convenient and inexpensive production the system’s earlier linker chemistry. purifies synthetic intermediates and final through automated synthesis. Also called The new chemistry also leaves a spacer products by using affinity chromatography glycans, these assemblies of linked sugar on the end of the final product’s terminal to hook onto fluorous tags added to the monomers are of immense importance sugar instead of removing it laboriously, as building blocks in a first step. biologically, but the difficulty of obtaining was done before. This terminal group can Monitoring solution-phase reactions is a them in pure form and constructing them be used to attach the oligosaccharide to lot easier than monitoring solid-phase reacfrom scratch has hampered their study. carbohydrate arrays, affinity beads, fluotions, Pohl and coworkers note. Another adApplications of oligosaccharide synthesis rescent markers, and quantum dots for a vantage, they say, is that new synthetic methinclude the development of carbohydraterange of research applications. ods, which are generally developed in solubased drugs and vaccines for a range of In the past, “we showed in principle that tion, are more readily translatable for use in a diseases, such as malaria and AIDS. automated synthesis works, but we made solution-phase automated synthesizer. In Division of To create their auCarbohydrate Chemtomated synthesizer, SUGAR ROAD Solution-phase automated synthesis scheme has iterative istry sessions at the the researchers modiglycosylation, deprotection, and extraction steps to construct oligosaccharides. American Chemified a Chemspeed cal Society national automated-synthesis O meeting in Salt Lake workstation. A robotCity last month, one ics platform delivers O researcher presented reagents to a reactor recent progress in vessel, runs a linksimplifying and fully age reaction for a O O automating a robotic set amount of time, solid-phase synthesis introduces a reactiontechnique his group quenching solution, Glycosylation Deprotection Fluorous solid-phase extraction had developed earlier. delivers deprotection ● Activating group Sugar building blocks ■ Fluorous tag And students from anreagents, concentrates other research group the product solution, discussed disease-related oligosaccharides few materials that could be used by biololoads it onto a fluorous solid-phase extracthey had constructed with a newly revealed gists. We have overcome that hurdle now,” tion cartridge, washes off reagents and any solution-phase approach. Seeberger said. unused building blocks, and elutes the linkPeter H. Seeberger of the Max Planck Ancora Pharmaceuticals, a Medford, age product. The product is then returned to Institute for Colloids & Interfaces, in Mass.-based company Seeberger coa reactor vessel, and the process is repeated Potsdam, Germany, has been creating biofounded, is creating beta-test models of the iteratively to add additional sugars. medically important oligosaccharides in automated solid-phase synthesizer for acaAt the ACS meeting, grad student Heather an automated fashion since 2000, when he demic research groups that have requested D. Spangler reported having carried out aufirst reported having modified a commerthem. Seeberger’s group and researchers at tomated solution-phase syntheses of key olicial peptide synthesizer to link monosacAncora have been using the synthesizer to gosaccharides from bacteria associated with charides together on polystyrene beads. develop carbohydrate vaccine candidates the skin disease cellulitis. And grad student In Salt Lake City he reported that his team active against malaria, leishmaniasis, and Shu-Lun (Ben) Tang reported on the first has now fully automated a solid-phase carbacterial infections. use of automated solution-phase synthesis bohydrate synthesizer and made it more to make β-linked mannose oligosaccharides, amenable for use by nonspecialists. MEANWHILE, students in Nicola L. Pohl’s which play a role in fungal infections. A key change is redesigned linker chemisgroup at Iowa State University, in Ames, Pohl and coworkers have started an autry, which simplifies and speeds the synthesis reported promising results with an autotomated carbohydrate synthesis company, and for the first time permits thioglycosides mated carbohydrate synthesis approach LuCella Biosciences, in Ames. Rather than to be used in the synthesizer. Thioglycosides in which all reactions occur in solution, selling instruments, the firm will provide are sugar monomers with sulfur-linked subinstead of on solid-phase beads. bespoke sugars for scientific research, likestituents; they are widely used in carbohyWith bead-based synthesizers, excess ly by the end of this year.—STU BORMAN WWW.CEN-ONLINE.ORG
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