Regiospecific phosphohydrolases from Dictyostelium as tools for the chemoenzymatic synthesis of the enantiomers D-myo-inositol 1,2,4-trisphosphate and D-myo-inositol 2,3,6-trisphosphate: non-physiological, potential analogues of biologically active D-myo-inositol 1,3,4-trisphosphate.
A new de novo synthesis of the enantiomeric pair D-myo-inositol 1,2,4-trisphosphate and D-myo-inositol 2,3,6-trisphosphate is described. Starting from enantiopure dibromocyclohexenediol, several C2 symmetrical building blocks were synthesized which gave access to D-myo-inositol 1,2,4,5-tetrakisphosphate and D-myo-inositol 1,2,3,6-tetrakisphosphate. Exploiting the high regiospecificity of two partially purified phosphohydrolases from Dictyostelium, a 5-phosphatase and a phytase, the inositol tetrakisphosphates were converted enzymatically to the target compounds. Their potential to modulate the activity of Ins3,4,5,6P4 1-kinase was investigated and compared with the effects of D-myo-inositol 1,3,4-trisphosphate.
Adelt
S
S
Institute für Biochemie und Organische Chemie, Bergische Universität Wuppertal, Gaussstrasse 20, 42097, Wuppertal, FRG.
Plettenburg
O
O
Dallmann
G
G
Ritter
F P
FP
Shears
S B
SB
Altenbach
H J
HJ
Vogel
G
G
D000818:Animals; D004023:Dictyostelium / Q000201:enzymology*; D007294:Inositol / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008968:Molecular Conformation; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D010770:Phosphotransferases / Q000187:drug effects / Q000378:metabolism
C440348:D-myo-inositol-1,2,4-trisphosphate; C440349:D-myo-inositol-1,3,4-trisphosphate; C440350:D-myo-inositol-2,3,6-trisphosphate; D007294:Inositol; D010770:Phosphotransferases; D010744:Phosphoric Monoester Hydrolases