Chemical methods for degradation of target proteins using designed light-activatable organic molecules

• Published in: Chemical communications (Cambridge, England) England), 2012-01, Vol.48 (62), p.7659-7671
• Main Authors: Tanimoto, Shuho, Takahashi, Daisuke, Toshima, Kazunobu
• Format: Article
• Language: English
• Subjects: Amyloid beta-Peptides - chemistry; Animals; Cell Line; Estrogen Receptor alpha - chemistry; Fullerenes - chemistry; HIV Protease - chemistry; Humans; Monosaccharides - chemistry; Photolysis; Photosensitizing Agents - chemical synthesis; Porphyrins - chemistry; Proteolysis; Quinolines - chemistry; Rats; Steroids - chemistry; Sulfonic Acids - chemistry; Ultraviolet Rays
• ISSN: 1359-7345; 1364-548X
• DOI: 10.1039/c2cc30831b

Molecular design, chemical synthesis, and biological evaluation of several designed organic molecules, which target-selectively degrade proteins upon photo-irradiation, are introduced. The designed molecules for protein photo-degradation include 2-phenylquinoline-steroid hormone hybrids and porphyrin derivatives, both of which selectively photo-degrade estrogen receptor-α, and fullerene-sugar and -sulfonic acid hybrids, which selectively photo-degrade HIV-1 protease and amyloid β, respectively. The information will provide a novel and effective way to control specific functions of proteins, and contribute to the molecular design of novel protein photo-degrading agents, which should find wide application in chemistry, biology, and medicine. In this feature article, the development of novel chemical agents, which can selectively degrade target proteins by irradiation with a specific wavelength of light under mild conditions without any additives, is introduced.