d- Glycero -β-d- manno heptose Phosphate 7- O -Modifications

• Published in: Journal of organic chemistry Vol. 86; no. 3; pp. 2184 - 2199
• Main Authors: Williams, Dean, Jamshidi, Mohammad P, St Michael, Frank, Chisholm, Kenneth, Cox, Andrew, Sauvageau, Janelle
• Format: Journal Article
• Language: English
• Published: United States 05-02-2021
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/acs.joc.0c02333

Pathogen-associated molecular patterns activate the immune system via pattern recognition receptors. Recently, newly discovered pathogen-associated molecular patterns, d-
-β-d-
heptose phosphate and d-
-β-d-
heptose 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-
-β-d-
heptose phosphate, d-
-β-d-
heptose 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-
-modifications of d-
-β-d-
heptose phosphate to produce molecular probes toward the development of a useful toolbox for biologists. A convergent strategy that involves introduction of a substituent at
-7 before alkene oxidation was investigated and proved successful in the generation of a range of molecular probes.