New glycosylation methods for microbial glycan synthesis

Ended Project Grant Awarded Last action

Award ID
R15GM147867
Recipient
Awarding agency
Obligated
$903,000

Award facts

Assistance listing
93.859 Biomedical Research and Research Training
Completion date
Originally
Place of performance
Ottawa Hills, OH 43606, USA

Award details come from USAspending.gov.

Description

Abstract
The emergence of drug resistant microbial strains has posed a great threat to the global human health. To prevent bacterial infections and reduce our reliance on antibiotic treatment, development of alternative effective approaches is extremely urgent. Invasive bacteria often produce unique and complex cell surface glycans, e.g. capsular polysaccharides (CPS), whose structures are significantly different from human glycome. These microbial glycans are essential virulence factors for pathogen invasion and promising targets for the development of effective vaccines for preventing bacterial infections. Glycan-based antimicrobial vaccines are often prepared by conjugation of capsular polysaccharides to a protein carrier. Currently, glycan antigens are mainly obtained from bacterial fermentation. Hence, IT is difficult to control the quality and length of glycans. In order to prepare homogeneous fully synthetic glycoconjugate vaccines, chemical synthesis remains as a reliable approach to access sufficient quantities and good purity of bacterial carbohydrate molecules. Structurally, microbial glycans often consists of unusual and highly complex monosaccharides as well as challenging glycosidic linkages. Therefore, their chemical synthesis demands the development of new efficient glycosylation methods and strategies. In this application, two new catalytic glycosylation methodologies will be developed including: 1) a cationic gold(i)-catalyzed glycosylation involving glycosyl n-1,1-dialkylpropargyl carbamate donors, and 2) a cesium-catalyzed anomeric o-alkylation for stereoselective construction of SS-mannoside type linkages. Synthesis of representative antigenic oligosaccharide repeating units from harmful bacteria, such as salmonella strains, bacillus anthracis and bacillus stearothermophilus will be carried out employing these newly developed glycosylation methods.

Transactions

Action Obligated Date
Amendment $0
Amendment $451,500
Original award $451,500

Quick answers

Who received award R15GM147867?

R15GM147867 was awarded to University Of Toledo by National Institute of General Medical Sciences (National Institutes of Health) on September 1, 2022.

How much is award R15GM147867 worth?

$903,000 has been obligated on R15GM147867.

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