Automation of Surface-Tethered Iterative Carbohydrate Synthesis (STICS) Project Summary Carbohydrates form the basis of all living organisms and, as a consequence, are ubiquitous both in nature as biologically active compounds and in medicine as therapeutics. Although there has been continued interest in the synthesis of carbohydrates, and the inherent complexity of these molecules consistently captures the attention of many scientists, methods for the isolation, chemical or enzymatic synthesis, analysis, and application of carbohydrates remain cumbersome. Ever-increasing time constraints and cost limitations on research and development in glycoscience and glycotechnology call for the development of rapid, efficient and operationally simple procedures. While this represents an immense task, as acknowledged in the recent National Academy of Sciences report Transforming glycoscience: a roadmap for the future, this proposal will focus on the introduction of a new, simple automation platform into the synthesis, evaluation, and application of carbohydrates on solid supports. Current automated methods for the synthesis of oligosaccharides are highly sophisticated, operationally complex, and require significant user know-how. On the other hand, high performance liquid chromatography (HPLC) equipment based automation introduced by our laboratories is by far a more attractive method. This is because almost all experimentalists have operational knowledge of and easy access to HPLC equipment. HPLC-assisted synthesis offers not only operational simplicity, but also convenient real-time reaction monitoring of every step using detectors and standard computer software and interface. We already achieved faster reaction times using less reactant, reagent and solvent than manual solid-phase synthesis. However, HPLC-based automation does have the inherent drawbacks of traditional solid-phase synthesis. Building upon promising preliminary results acquired during the development of HPLC-based and STICS approaches, this proposal aims to generate a user-friendly, universal platform for automated and monitored synthesis. This proposal is organized into four Specific Aims dedicated to: 1) new concepts for chemical glycosylation; 2) the refining of all aspects of HPLC-assisted synthesis; 3) the preparation and application of nanoporous materials as solid supports; and 4) the development of synthetic and analytical tools for studying tumor- associated markers. Upon completion of the proposed studies, we expect to have acquired a reliable and simple platform for automated oligosaccharide synthesis. Many classes of compounds can be obtained using solid supports; therefore, the proposed study is expected to be of valuable methodological and practical use to all scientists. Practically anyone with access to basic HPLC equipment should be able to perform automated synthesis and real-time reaction monitoring. Synthesis of carbohydrates and other classes of biomolecules using this user-friendly, automated platform will accelerate discovery in many scientific disciplines and, hence, significantly impact technology, society, the economy and human health.

Public Health Relevance

Automation of Surface-Tethered Iterative Carbohydrate Synthesis (STICS) Project Narrative The proposed research will deliver an automated approach to accelerate and broaden access to carbohydrate structures needed for biological studies aimed at enhancing the understanding of serious diseases including many different cancers, autoimmune diseases, and bacterial infections. Increasing the availability of these molecules for biological studies will aid efforts o develop carbohydrate-based therapeutic and diagnostic agents.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
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Lees, Robert G
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University of Missouri-St. Louis
Schools of Arts and Sciences
Saint Louis
United States
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Bhattarai, Jay K; Neupane, Dharmendra; Nepal, Bishal et al. (2018) Preparation, Modification, Characterization, and Biosensing Application of Nanoporous Gold Using Electrochemical Techniques. Nanomaterials (Basel) 8:
O'Neil, Crystal L; Stine, Keith J; Demchenko, Alexei V (2018) Immobilization of glycans on solid surfaces for application in glycomics. J Carbohydr Chem 37:225-249
Wang, Tinghua; Nigudkar, Swati S; Yasomanee, Jagodige P et al. (2018) Glycosyl nitrates in synthesis: streamlined access to glucopyranose building blocks differentiated at C-2. Org Biomol Chem 16:3596-3604
Singh, Yashapal; Wang, Tinghua; Geringer, Scott A et al. (2018) Regenerative Glycosylation. J Org Chem 83:374-381
Hasty, Scott J; Rath, Nigam P; Demchenko, Alexei V (2017) Extending the S-benzimidazolyl (SBiz) platform: N-alkylated SBiz glycosyl donors with the universal activation profile. Pure Appl Chem 89:1321-1331
Stine, Keith J (2017) Enzyme Immobilization on Nanoporous Gold: A Review. Biochem Insights 10:1178626417748607
Stine, Keith J (2017) Application of Porous Materials to Carbohydrate Chemistry and Glycoscience. Adv Carbohydr Chem Biochem 74:61-136
Nigudkar, Swati S; Wang, Tinghua; Pistorio, Salvatore G et al. (2017) OFox imidates as versatile glycosyl donors for chemical glycosylation. Org Biomol Chem 15:348-359
Bandara, Mithila D; Yasomanee, Jagodige P; Rath, Nigam P et al. (2017) Conformationally superarmed S-ethyl glycosyl donors as effective building blocks for chemoselective oligosaccharide synthesis in one pot. Org Biomol Chem 15:559-563
Jia, Xiao G; Demchenko, Alexei V (2017) Intramolecular glycosylation. Beilstein J Org Chem 13:2028-2048

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