Glycosphingolipids are essential components of human plasma membrane. More than 300 glycosphingolipid glycans have been characterized. The glycans are directly involved in molecular recognition event. A number of cancer-associated glycosphingolipid glycans are being developed as cancer vaccines. Most glycosphingolipid glycans are not commercially available. The costs for a limited number of commercially available ones are extremely high. We have developed highly effective one-pot multienzyme (OPME) approaches for high-yield and cost-effective production of complex glycans. The OPME approaches will be used in generating a library of 60 structurally diverse glycosphingolipid glycans including those contain different naturally occurring sialic acid forms.
Three specific aims are to synthesize 1) ganglio-series;2) lacto- and neolacto-series;and 3) globo- and isoglobo-series glycosphingolipid glycans using our established high efficient OPME strategies. Each of the 60 compounds will be synthesized under GLP conditions in 10-50 mg scale, purified to >98% purity, and characterized by nuclear magnetic resonance spectroscopy (NMR) and high-resolution mass spectrometry (HRMS). For all glycans synthesized (>98% purityL 50 micrograms of each will be sent to an NIGMS-designed screening center for validation testing, glycan microarray and other screening assays. These glycans are essential standards and invaluable probes for bioassays and biomedical applications.

Public Health Relevance

Glycosphingolipid head groups will be synthesized and characterized. These carbohydrates are essential standards for structural analysis and critical probes for bioassays and biomedical studies for developing novel carbohydrate-based diagnostics and therapeutics.

Agency
National Institute of Health (NIH)
Type
Small Business Innovation Research – Phase I (N43)
Project #
261201300041C-0-0-1
Application #
8758478
Study Section
Project Start
2013-09-12
Project End
2014-06-11
Budget Start
Budget End
Support Year
Fiscal Year
2013
Total Cost
$298,447
Indirect Cost
Name
Glycohub, Inc.
Department
Type
DUNS #
078632717
City
Woodland
State
CA
Country
United States
Zip Code
95776