Thymidine phosphorylase from Escherichia coli:: Tight-binding inhibitors as enzyme active-site titrants

被引：20

作者：

Gbaj, A ^{[1
]}

Edwards, PN ^{[1
]}

Reigan, P ^{[1
]}

Freeman, S ^{[1
]}

Jaffar, M ^{[1
]}

Douglas, KT ^{[1
]}

机构：

[1] Univ Manchester, Sch Pharm & Pharmaceut Sci, Wolfsan Ctr Rat Struct Based Design Mol Diagnost, Manchester M13 9PL, Lancs, England

来源：

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY | 2006年 / 21卷 / 01期

关键词：

stoichiometric inhibition; inhibitors; angiogenesis; anticancer drugs; transition state inhibitor; thymidine phosphorylase;

D O I：

10.1080/14756360500424010

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Thymidine phosphorylase (EC 2.4.2.4) catalyses the reversible phosphorolysis of pyrimidine 2-deoxynucleosides, forming 2-deoxyribose-1-phosphate and pyrimidine. 5-Chloro-6-(2-imino-pyrrolidin-1-yl)methyl-uracil hydrochloride (TPI, 1) and its 5-bromo analogue (2), 6-(2-amino-imidazol-1-yl)methyl-5-bromo-uracil (3) and its 5-chloro analogue (4) act as tight-binding stoichiometric inhibitors of recombinant E. coli thymidine phosphorylase, and thus can be used as the first active-site titrants for it using either thymidine or 5-nitro-2'-deoxyuridine as substrate.

引用

页码：69 / 73

页数：5

共 32 条

[1] The role of thymidine phosphorylase,, an angiogenic enzyme, in tumor progression [J].

Akiyama, S ;

Furukawa, T ;

Sumizawa, T ;

Takebayashi, Y ;

Nakajima, Y ;

Shimaoka, S ;

Haraguchi, M .

CANCER SCIENCE, 2004, 95 (11) :851-857

[2] IRREVERSIBLE ENZYME INHIBITORS .167. THYMIDINE PHOSPHORYLASE .10. ON NATURE AND DIMENSIONS OF HYDROPHOBIC BONDING REGION .2. [J].

BAKER, BR ;

HOPKINS, SE .

JOURNAL OF MEDICINAL CHEMISTRY, 1970, 13 (01) :87-&

[3] Nucleophilic participation in the transition state for human thymidine phosphorylase [J].

Birck, MR ;

Schramm, VL .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2004, 126 (08) :2447-2453

[4]

BRADFORD MM, 1976, ANAL BIOCHEM, V72, P248, DOI 10.1016/0003-2697(76)90527-3

[5]

Brown NS, 1998, BIOCHEM J, V334, P1

[6]

Cole C, 1999, ANTI-CANCER DRUG DES, V14, P383

[7]

Cole C, 1999, ANTI-CANCER DRUG DES, V14, P411

[8] Potential tumor-selective nitroimidazolylmethyluracil prodrug derivatives: Inhibitors of the angiogenic enzyme thymidine phosphorylase [J].

Cole, C ;

Reigan, P ;

Gbaj, A ;

Edwards, PN ;

Douglas, KT ;

Stratford, IJ ;

Freeman, S ;

Jaffar, M .

JOURNAL OF MEDICINAL CHEMISTRY, 2003, 46 (02) :207-209

[9] Design, synthesis, and enzymatic evaluation of multisubstrate analogue inhibitors of Escherichia coli thymidine phosphorylase [J].

Esteban-Gamboa, A ;

Balzarini, J ;

Esnouf, R ;

De Clercq, E ;

Camarasa, MJ ;

Pérez-Pérez, MJ .

JOURNAL OF MEDICINAL CHEMISTRY, 2000, 43 (05) :971-983

[10] Thymidine Phosphorylase: A Two-Face Janus in Anticancer Chemotherapy [J].

Focher, F. ;

Spadari, S. .

CURRENT CANCER DRUG TARGETS, 2001, 1 (02) :141-153

← 1 2 3 4 →