Alternate synthesis to d-glycero-β-d-manno-heptose 1,7-biphosphate

Abstract

d-glycero-β-d-manno-heptose 1,7-biphosphate (HBP) is an enzymatic intermediate in the biosynthesis of the heptose component of lipopolysaccharide (LPS), and was recently revealed to be a pathogen-associated molecular pattern (PAMP) that allows detection of Gram-negative bacteria by the mammalian immune system. Cellular detection of HBP depends upon its stimulation of a cascade that leads to the phosphorylation and assembly of the TRAF-interacting with forkhead-associated domain protein A (TIFA), which activates the transcription factor NF-κB. In this note, an alternate chemical synthesis of HBP is described and its biological activity is established, providing pure material for further assessing and exploiting the biological activity of this compound.

Keywords: Nuclear factor-kappa B (NF-κB); Pathogen-associated molecular pattern (PAMP); TRAF-interacting with forkhead-associated domain protein A (TIFA); Wittig reaction; d-glycero-β-d-manno-heptose 1,7-biphosphate (HBP).