Carbohydrates are key to understanding and ultimately modulating host-pathogen interactions, but the study of these interactions has been hampered by access to well-defined glycan structures. The overall goals of this project, in response to RFA-GM-09-005 """"""""Expanding the Chemical Space of Carbohydrates,"""""""" are to develop quick routes to several key glycan building blocks, develop methods for the automated solution-phase synthesis of biologically important structures that contain not only common but also particularly difficult glycosidic linkages, and to develop a new tool using these synthetic glycans to identify protein partners of oligosaccharides on, for example, the surface of pathogenic bacteria.
The specific aims of the proposed project are to: 1) develop methods for the automated syntheses of beta-glucosides and one of the most challenging glycosidic linkages-beta-mannosides-and apply these methods to the automated syntheses of fungally-associated glucans and mannans;2) develop methods for the automated synthesis of the highly branched sugars found on the cell surface of the nematode C. elegans that are key to infectivity by various bacterial pathogens;3) develop methods for the automated synthesis of uronic acid-containing repeating oligosaccharides and apply these methods to the synthesis of certain bacterial capsular polysaccharides and glycosaminoglycans;and 4) develop a new solid-phase-based cross-linking reagent that can incorporate these glycan products of the automated synthesis platform to identify carbohydrate binding proteins by mass spectrometry.
Carbohydrates are key to host-pathogen interactions, but their study has been limited because pure oligosaccharides are hard to obtain. The overall goals of this project, in response to RFA- GM-09-005 """"""""Expanding the Chemical Space of Carbohydrates,"""""""" are to develop quick routes to several key carbohydrate building blocks, develop methods for the automated solution-phase synthesis of biologically important structures that contain not only common but also particularly difficult glycosidic linkages, and to develop a new tool using these synthetic glycans to identify protein partners of oligosaccharides.
