Nuclear receptors mediate allosteric
communications where ligand binding initiates a
cascade of signal transduction. The interaction of
vitamin D with vitamin D receptor (VDR) was
investigated by
19F NMR spectroscopy of the
complexes of three fluorinated vitamin D
derivatives with the full-length rat VDR-LBD. In the
19F NMR spectra of the VDR-ligand complexes, the
A-ring of 4,4-difluoro-1,25(OH)
2D
3 was revealed to
adopt β-conformation in the VDR in solution, and
the spectra were shown to be dependent on the
dissociation constant. While the complex of
4,4-difluoro-1,25(OH)
2D
3 with VDR exhibited a
clear distinguishable
19F NMR spectrum, those of
19F-1,25(OH)
2D
3 stereoisomers, which have 10-fold
higher VDR affinity than 4,4-difluoro-1,25(OH)
2D
3,
did not. The solid-phase NMR technique was useful
for
19F-1,25(OH)
2D
3 stereoisomers. The fluorinated
vitamin D derivatives showed marked changes in
the chemical shift (Δ4−19.7 ppm) upon VDRcomplex
formation, and the ab initio MO method
suggested that van der Waals interactions play a
major role in the complex formation
抄録全体を表示