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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
1R01GM090280-01
Application #
7792581
Study Section
Special Emphasis Panel (ZGM1-PPBC-3 (CS))
Program Officer
Marino, Pamela
Project Start
2009-09-30
Project End
2013-08-31
Budget Start
2009-09-30
Budget End
2010-08-31
Support Year
1
Fiscal Year
2009
Total Cost
$289,351
Indirect Cost
Name
Iowa State University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
005309844
City
Ames
State
IA
Country
United States
Zip Code
50011
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