Photoaffinity Analogue for the Anti-inflammatory Drug α-Trinositol: Synthesis and Identification of Putative Molecular Targets

Publisher Website
Google Scholar
Abstract
α-Trinositol (αT), or Ins(1,2,6)P3, is a semisynthetic inositol trisphosphate produced commercially by the partial degradation of phytic acid with phytase. The molecular targets mediating the mechanism of action of this novel anti-inflammatory, analgesic, and antivasoconstrictive drug are unknown. A new photoaffinity analogue, 4-[3H]BZDC-αT, has been prepared in which the [3H]-p-benzoyldihydrocinnamoyl ([3H]BZDC) photophore is tethered through an O-(5-aminopentanoyl) linkage to the 4-OH of αT. Photoaffinity labeling experiments with two human tissues, umbilical cord vascular smooth muscle cells and platelet membranes, revealed proteins that were selectively labeled by 4-[3H]BZDC-αT. Thus, co-incubation with αT but not with Ins(1,3,4,5)P4 during photolysis competitively displaced labeling of a 55 kDa platelet protein. In vascular epithelial cells, αT and Ins(1,3,4,5)P4 both displaced labeling of a 55 and 43 kDa proteins. The identification of putative protein targets for αT in smooth vascular tissue may have important implications in elucidation of the mechanism of action of this unusual drug.