Journal of Medicinal Chemistry p. 11 - 14 (1984)
Update date:2022-07-30
Topics:
Ajmera, Sudhir
Bapat, Ashok R.
Danenberg, Kathleen
Danenberg, Peter V.
5-Fluoro-2',3'-dideoxy-3'-fluorouridine (3'-FFdUrd) and 5-fluoro-2',3'-dideoxy-3'-fluorouridine 5'-phosphate (3'-FFdUMP) have been synthesized, and their interactions with thymidine (dThd) phosphorylase and thymidylate (dTMP) synthetase, respectively, have been examined. 3'-FFdUrd is not a substrate for dThd phosphorylase, but is a weak, noncompetitive inhibitor (Ki = 1.7 mM). 3'-FFdUMP inhibits dTMP synthetase competitively with deoxyuridylate (Ki = 0.13 mM) when both the substrate and inhibitor are present simultaneously.However, in the presence of 5,10-methylenete trahydrofolate, the inhibition increases with time in a first-order manner (konobsd = 0.029 s-1).A complex is formed between <6-3H>3'-FFdUMP and dTMP synthetase, which is isolable on nitrocellulose filters, and has a dissociation rate (koffobsd = 1.4*10-2 min-1) similar to that of the potent inhibitor 5-fluoro-2'-deoxyuridilate (koffobsd = 1.3*10-2 min-1) from its ternary complex with dTMP synthetase.These results are explained in terms of a two-stage model involving the initial formation of a revesible adsorption complex, followed by a slow conversion to a tight-binding catalytic complex.
View MoreTianjin Chemsyntech Chemical Co., Ltd
Contact:+86-22-60872258
Address:Haitai green industry base in Tianjin, K1,5-601
website:http://www.shochem.com
Contact:021-50800795
Address:No.1043, Halei Rd, Zhangjiang Hi-Tech Park, Shanghai, Postcode 201203, China
Hangzhou yi lu biont technology Co., LTD
Contact:+86-571-88152630
Address:Hangzhoushi HuafengRoad Yicheng3Building1001room.
Ningbo Distant Chemicals Co.,Ltd
Contact:86-574-27862490,27862438
Address:5F-3,#54 DaShaNi street,Ningbo,CHINA
Penglai Qianwei Chemical Co., Ltd.
Contact:86-535-3357802
Address:Shahelu (north), Penglai, Shandong, China
Doi:10.1021/ja01587a044
(1956)Doi:10.1039/b513189h
(2005)Doi:10.1016/j.tetlet.2010.11.086
(2011)Doi:10.1016/j.jfluchem.2009.04.010
(2009)Doi:10.1021/ml100289m
(2011)Doi:10.1016/j.ejmech.2010.10.010
(2011)