Tuesday, May 7, 2024
5/7/2024
Project Summary Carbohydrates form the basis of all living organisms and are ubiquitous both in nature and in medicine. However, methods for the chemical synthesis of carbohydrates remain cumbersome. The rapid growth of R&D in glycoscience demands the development of rapid, efficient, and simple procedures for glycan synthesis. This proposal seeks to meet this demand by focusing on the development of an affordable and accessible automation platform that will enable both specialists and non-specialists to perform the synthesis of glycans from renewable precursors. Current methods for the synthesis of glycans are highly sophisticated and operationally complex. By contrast, high performance liquid chromatography equipment-based automation (HPLC-A) represents a highly accessible method for synthesis because many scientists already have easy access to HPLC equipment. Automated synthesis offers operational simplicity by delivering all reagents using standard HPLC components, but also convenient real-time reaction monitoring of every step. Some of our automated reactions have been accurately reproduced by a minimally trained high-school student researcher. Unexpected recent pandemic revealed unpreparedness of our society, but also gave us an opportunity to showcase how HPLC-A can be utilized to enhance our productivity. This proposal aims to improve our HPLC-A setup by introducing a universal platform for completely automated synthesis of glycans from simple and renewable precursors. We propose to develop a dedicated automated circuit for the synthesis of sugar building blocks and will develop dedicated glycosylation methods that will connect monosaccharides into oligomeric networks in the automated setting modes for syntheses on solid supports and in solution. We will accessorize our system with new modules and attachments to achieve high efficiency of synthetic steps, improve reproducibility of reactions, help to reduce reagent and solvent excess. We will then demonstrate how well these strategic adjustments work in the completely automated, “press of a button” production of glycans. We are currently interested in glycans found in human milk, but the developed methods and technologies will also allow to achieve other sequences. Upon completion of the proposed studies, we expect to have achieved a reliable and simple platform for completely automated synthesis of glycans from simple and renewable precursors. Investigators with access to standard HPLC equipment should be able to perform automated synthesis using our methods. Machine- assisted synthesis ensures rigorous experimental design to obtain robust results, to eliminate variability, and to accurately reproduce experiments multiple times by different users. Synthesis of glycans using this user- friendly, automated platform will accelerate discovery in many scientific disciplines and can significantly impact technology, society, the economy, and public health.
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