d -Glycero-β-d -mannoheptose Phosphate 7-O-Modifications
| Autor: | Frank St. Michael, Kenneth Chisholm, Janelle Sauvageau, Mohammad P. Jamshidi, Dean Williams, Andrew D. Cox |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
phosphates
reaction products 010405 organic chemistry Chemistry Organic Chemistry Pattern recognition receptor 010402 general chemistry Phosphate 01 natural sciences 0104 chemical sciences chemistry.chemical_compound D-mannoheptose Immune system post-translational modification Biochemistry hydrocarbons organic compounds |
| Zdroj: | The Journal of Organic Chemistry. 86:2184-2199 |
| ISSN: | 1520-6904 0022-3263 |
| DOI: | 10.1021/acs.joc.0c02333 |
| Popis: | Pathogen-associated molecular patterns activate the immune system via pattern recognition receptors. Recently, newly discovered pathogen-associated molecular patterns, d-glycero-β-d-mannoheptose phosphate and d-glycero-β-d-mannoheptose 1,7-biphosphate, were shown to induce a TRAF-interacting protein with a forkhead-associated domain-dependent immune response in human embryonic kidney cells and colonic epithelial cells. Concurrently, ADP-heptose was shown to bind α-kinase 1 and activate TIFA via phosphorylation leading to an immune cascade to ultimately activate NF-κB. These pathogen-associated molecular patterns have raised interest in the pharmaceutical industry for their potential use as immunomodulators. However, little is understood about the host cell uptake of d-glycero-β-d-mannoheptose phosphate, d-glycero-β-d-mannoheptose 1,7-biphosphate, and ADP-heptose in vivo and derivatives of these molecules are needed to interrogate this. In this regard, herein we describe 7-O-modifications of d-glycero-β-d-mannoheptose phosphate to produce molecular probes toward the development of a useful toolbox for biologists. A convergent strategy that involves introduction of a substituent at O-7 before alkene oxidation was investigated and proved successful in the generation of a range of molecular probes. |
| Databáze: | OpenAIRE |
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