[Structure-activity relationship of novel vitamin K analogues as steroid and xenobiotic receptor (SXR) agonists].

Vitamin K2 is a ligand for a nuclear receptor, steroid and xenobiotic receptor (SXR), that induces the gene expressions of CYP3A4. We synthesized new vitamin K analogues with the same isoprene side chains symmetrically introduced at the 2 and 3 positions of 1,4-naphthoquinone and vitamin K2 analogues with hydroxyl or phenyl groups at the ω-terminal of the side chain. The upregulation of SXR-mediated transcription of the target gene by the analogues was dependent on the length of the side chain and the hydrophobicity of the ω-terminal residues.

Synthesis of new vitamin K analogues as steroid and xenobiotic receptor (SXR) agonists: insights into the biological role of the side chain part of vitamin K.

Vitamin K(2) has been demonstrated to induce gene expression related to bone formation through a nuclear steroid and xenobiotic receptor (SXR). We synthesized new vitamin K analogues with the same isoprene side chains symmetrically introduced at the 2 and 3 positions of 1,4-naphthoquinone and evaluated the transcriptional activity of the target gene. The transcriptional activity was related to the length of the side chain which allowed optimal interaction with ligand-binding domain of SXR.

Ligand-dependent conformation change reflects steric structure and interactions of a vitamin D receptor/ligand complex: a fragment molecular orbital study.

We used an in silico computational method to theoretically analyze important residue-ligand interactions as well as ligand conformation changes in the vitamin D receptor (VDR). The ligand used for analysis was 1alpha,25-dihydroxy-19-nor-vitamin D3 [1alpha,25-19-nor-(OH)2D3] [1,2], whose crystal structure has not been solved. To estimate amino acid residue-ligand interactions with chemical accuracy, we adopted the fragment molecular orbital (FMO) method [3,4], which is based on the nonempirical total electronic quantum calculation.