Photocontrol of the mitotic kinesin Eg5 using a novel S-trityl-L-cysteine analogue as a photochromic inhibitor.
Because the mitotic kinesin Eg5 is essential for the formation of bipolar spindles during eukaryotic cell division, it has been considered as a potential target for cancer treatment. A number of specific and potent inhibitors of Eg5 are known. S-trityl-L-cysteine is one of the inhibitors of Eg5 whose molecular mechanism of inhibition was well studied. The trityl group of S-trityl-L-cysteine was shown to be a key moiety required for potent inhibition. In this study, we synthesized a novel photochromic S-trityl-L-cysteine analogue, 4-(N-(2-(N-acetylcysteine-S-yl) acetyl) amino)-4'- (N-(2-(N-(triphenylmethyl)amino)acetyl)amino)azobenzene (ACTAB), composed of a trityl group, azobenzene and N-acetyl-L-cysteine, which exhibits cis-trans photoisomerization in order to photocontrol the function of Eg5. ACTAB exhibited cis-trans photoisomerization upon alternating irradiation at two different wavelengths in the visible range, 400 and 480 nm. ACTAB induced reversible changes in the inhibitory activity of ATPase and motor activities correlating with the cis-trans photoisomerization. Compared with cis-ACTAB, trans-ACTAB reduced ATPase activity and microtubule gliding velocity more significantly. These results suggest that ACTAB could be used as photochromic inhibitor of Eg5 to achieve photocontrol of living cells.
Division of Bioengineering, Graduate School of Engineering, Soka University, Hachioji, Tokyo 192-8577, Japan; Deprtment of Bioengineering, Faculty of Engineering, Soka University, Hachioji, Tokyo 192-8577, Japan; and Division of Applied Bioscience, Graduate School of Agriculture, Hokkaido University, Sapporo 060-8589, Japan.
Kumiko
K
Ishikawa
Kanako
K
Tohyama
Shinya
S
Mitsuhashi
Shinsaku
S
Maruta
D000042:Absorption; D000818:Animals; D001391:Azo Compounds / Q000737:chemistry; D003545:Cysteine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D007536:Isomerism; D016547:Kinesins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007700:Kinetics; D008027:Light; D051379:Mice; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D008938:Mitosis / Q000187:drug effects*; D055668:Photochemical Processes; D013057:Spectrum Analysis; D034421:Sus scrofa
D001391:Azo Compounds; C003724:3-tritylthio-L-alanine; C521052:Kif11 protein, mouse; D016547:Kinesins; C009850:azobenzene; D003545:Cysteine
Eg5; inhibitor; kinesin; photochromic molecule; photocontrol