Research Terms
Ends | Title |
05-2024 |
Development of New Vaccine Adjuvants
Development of New Vaccine Adjuvants
NATL INST OF HLTH NIAI
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03-2024 |
NIH/NIGMS MIRA - Synthesis and Biology of GPIs
NIH/NIGMS MIRA - Synthesis and Biology of GPIs
NATL INST OF HLTH NIGM
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06-2021 |
Chemoenzymatic Synthesis and Biochemical Studies of Glycosphingolipids
Chemoenzymatic Synthesis and Biochemical Studies of Glycosphingolipids
NATL SCIENCE FO
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11-2020 |
Metabolic Engineering of Cancer for Selective Immunotargeting (NIH/NCI: 5R01CA095142-14)
Metabolic Engineering of Cancer for Selective Immunotargeting (NIH/NCI: 5R01CA095142-14)
NATL INST OF HLTH NC
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12-2018 |
New Methods to Access GPI-Anchored Proteins and Study GPI-Anchored Proteomics
New Methods to Access GPI-Anchored Proteins and Study GPI-Anchored Proteomics
NATL INST OF HLTH NIGM
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This strategy enables the diversity-oriented synthesis of various glycosphingolipids (GSLs). GSLs are a family of glycolipids with a sphingoid or a ceramide as the hydrophobic moiety linked to the downstream end of a carbohydrate chain through a glycosidic bond. GSLs are an essential component of the cell membrane and play a key role in many biological and pathological processes. Aberrant GSL expression and metabolism are associated with diseases such as cancer, diabetes, sclerosis, bacterial and viral infections, and Alzheimer’s disease, so exploring GSLs and their derivatives is popular in medical research. For example, neuroblastoma tumors surround themselves with orders of magnitude higher concentrations of GSLs, providing a target for treatment with monoclonal antibodies. However, the isolation of GSLs from nature is challenging, and it is only possible to obtain them in minor quantities. Chemical or enzymatic synthesis of GSLs is a promising alternative pathway to GSLs. However, these strategies suffer from low yields, high economic cost, poor solubility in water solutions, compatibility problems, and only provide individual structures one by one.
Researchers at the University of Florida have developed a strategy for high-yield synthesis of glycosphingolipids. This strategy combines chemical transformations and stepwise enzymatic elongations, rapidly producing diverse natural and functionalized glycolipids. These functional products can help achieve breakthroughs in research targeting specific cancers and degenerative diseases.
Diversity-oriented synthesis of glycosphingolipids important for diagnostic and biological applications, combining chemical and enzymatic transformations
This three-stage series of chemoenzymatic reactions efficiently synthesizes glycosphingolipids (GSLs). The first step involves the synthesis of a common GSL precursor by binding a protected mono- or disaccharide donor to a short lipid head via glycosylation and deprotection of the donor. The second step assembles a glycan in aqueous media through enzymatic elongation of the sugar chain. The final step comprises chemoselective reactions to construct the ceramide moiety on site. These reactions include metathesis to install the main lipid chain and azide reduction and acylation to install the N-linked lipid chain. All syntheses start or go through the same intermediates, making the process simple and reproducible. Furthermore, the synthesized GSLs may incorporate different lipids or functional groups, enabling a wide range of resulting GSL derivatives that may have valuable applications in drug development and medical and biological research.
This liquid chromatography, tandem mass spectrometry (LC-MS/MS) system utilizes an extensive mass spectrometry database and a two-step searching procedure to identify glycolipids and glycosphingolipids. Glycolipids play an important role in various physiological and pathological processes. More than 80 percent of glycan cells in the central nervous system are glycolipids related to many diseases such as cancer, Alzheimer’s disease, and depression. Identifying glycolipids in experimental samples remains challenging because of their unique chemical and physical properties. Available commercial software designed to identify lipids is not well suited for glycolipid analysis, especially for analysis of unknown glycolipids, since many glycolipids are absent from mass spectrometry libraries.
Researchers at the University of Florida have developed a tandem mass spectrometry system employing a more extensive library/database and a two-step process to search and identify specific glycolipids. The system analyzes the glycolipids and glycosphingolipids in bodily fluids and tissues to help identify biomarkers useful for diagnosis and therapy of diseases such as cancer, Alzheimer’s, or depression.
Improved mass spectrometry database and searching software that better identifies glycolipids and glycosphingolipids in tissue samples in order to develop biomarkers and therapeutic tools
The liquid chromatography, tandem mass spectrometry (LC-MS/MS) software applies a two-step process to analyze specific glycolipids, including glycosphingolipids, using an extensive database. The first step identifies the glycan moiety, and the second step identifies the lipid moiety. The mass spectrometry database will provide the tandem spectra to identify various glycolipids. Once the system obtains the MS/MS spectra of a sample, analysis using the database and new searching procedure identifies the glycolipid composition in terms of both glycan forms and lipid forms. The analytical system identifies glycolipids more efficiently than available commercial software designed for identifying lipids.