| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Research Abstract |
The goal of this study is to develop the analgesics based on novel antagonistmolecular mechanisms of the algesic nociceptin receptor, but not on ordinary agonist mechanisms of the analgesic opioid receptors. To set and achieve this goal, we performed
(1) alanine scanning of allamino acids of the receptor
(2) affinity labeling, and
(3) molecular modeling.
We have succeeded in preparations of all of possible point-mutated receptors one-by-one, and also in preparations of the affinity ligands for them. These enabled to identify three essential Cys residues present in the ligand-binding cavity. Their mapping on the modeling 3D-structure suggested that neighboring Tyr is a key residue for the antagonist binding.
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