Inhibition of 4-hydroxyphpenylpyruvate dioxygenase

• Main Author: 林東伸
• Other Authors: 楊定亞
• Format: Others
• Language: zh-TW
• Published: 1998
• Online Access: http://ndltd.ncl.edu.tw/handle/11084493260202243290

碩士 === 東海大學 === 應用化學研究所 === 86 === 　　The purification of 4-hydroxyphenylpyruvate dioxygenase (4-HPPD) from pig liver was accomplished. A series of 3-fluoro-phenylpyruvate derivatives were synthesized and the kinetic studies showed all of them were noncompetitive inhibitors of 4-HPPD. This result indicated that 4-HPPD has higher steric demands with regard to the structure of α-C is sp3(tetrahedron) instead of sp2(planar) hybridization, or there is a relatively bulky substituent on β-C position. Kinetic studies showed both 36 and 37 were noncompetitive inhibitors of 4-HPPD, whereas 38 was not an inhibitor at all. This evidence supported the assumption that the favoured keto-enol form of NTBC mimics the ketoacid functionality present in the substrate and is capable of binding strongly to the ferrous ion in the active site. Finally, two good competitive inhibitors i.e. 40a and 40c of 4-HPPD have been found with the Ki within μM range.