Logical design of medical chaperone for prion diseases.
A strategy of logical drug design (LDD) and its application to prion diseases are reviewed. LDD is primarily based on the localizability of a hot spot which initiates structural instability in the target protein. It is also based on the regulability of the hot spot by small compounds, their designabilty by a computer, their organic synthesizability and the specificity of their functions once administered to the biological organisms. Unification of localizability, regulability, producibility and specificity is the central theme of LDD. Theoretical foundation of LDD based on quantum theories is initially outlined. The localizability using nuclear magnetic resonance (NMR), the regulability by a medical chaperone, the synthesizability, and the functional specificity accomplished thus far, are then described.
United Graduate School of Drug Discovery and Medical Information Sciences, Department of Gene and Development, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu 501-1194, Japan. kuwata@gifu-u.ac.jp.
Kazuo
K
Kuwata
D000818:Animals; D015195:Drug Design; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D017096:Prion Diseases / Q000188:drug therapy*; D011328:Prions / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism / Q000472:pathogenicity; D011789:Quantum Theory
D018832:Molecular Chaperones; D011328:Prions