Synthesis, acid-base behavior, and binding properties of 6-modified myo-inositol 1,4,5-tris(phosphate)s

S Ballereau; P Guédat; S N Poirier; G Guillemette; B Spiess; G Schlewer

doi:10.1021/jm991084t

Synthesis, acid-base behavior, and binding properties of 6-modified myo-inositol 1,4,5-tris(phosphate)s

J Med Chem. 1999 Nov 18;42(23):4824-35. doi: 10.1021/jm991084t.

Authors

S Ballereau¹, P Guédat, S N Poirier, G Guillemette, B Spiess, G Schlewer

Affiliation

¹ Laboratoire de Pharmacochimie de la Communication Cellulaire UMR 7081 du CNRS, Faculté de Pharmacie, 74, route du Rhin, 67401 Illkirch, France.

PMID: 10579845
DOI: 10.1021/jm991084t

Abstract

myo-Inositol 1,4,5-tris(phosphate) was modified at position 6. The analogues synthesized are reported in this publication are 6-deoxy-myo-inositol 1,4,5-tris(phosphate), 6-fluoro-6-deoxy-myo-inositol 1,4,5-tris(phosphate), epi-inositol 1, 4,5-tris(phosphate), and 6-amino-6-deoxy-myo-inositol 1,4, 5-tris(phosphate). These derivatives showed poor affinity for the Ins(1,4,5)P(3) receptors. The inframolecular acid-base behavior and the cooperative effects between the phosphate groups could help explain the loss of affinity of these 6-modified analogues.

MeSH terms

Adrenal Cortex / ultrastructure
Animals
Calcium Channels / metabolism
Cattle
Hydrogen-Ion Concentration
In Vitro Techniques
Inositol 1,4,5-Trisphosphate / analogs & derivatives*
Inositol 1,4,5-Trisphosphate / chemical synthesis
Inositol 1,4,5-Trisphosphate / chemistry*
Inositol 1,4,5-Trisphosphate / metabolism
Inositol 1,4,5-Trisphosphate Receptors
Magnetic Resonance Spectroscopy
Microsomes / metabolism
Potentiometry
Receptors, Cytoplasmic and Nuclear / metabolism
Stereoisomerism

Substances

Calcium Channels
Inositol 1,4,5-Trisphosphate Receptors
Receptors, Cytoplasmic and Nuclear
Inositol 1,4,5-Trisphosphate