ChemInform Abstract: Novel Inhibitors of Trypanosoma cruzi Dihydrofolate Reductase.

ChemInform ◽  
2010 ◽  
Vol 32 (49) ◽  
pp. no-no
Author(s):  
Fabio Zuccotto ◽  
Marketa Zvelebil ◽  
Reto Brun ◽  
Shafinaz F. Chowdhury ◽  
Raffaella Di Lucrezia ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Dihydrofolate Reductase

The structure-based design and synthesis of selective inhibitors of trypanosoma cruzi dihydrofolate reductase

1999 ◽  
Vol 9 (10) ◽  
pp. 1463-1468 ◽  
Author(s):  
Fabio Zuccotto ◽  
Reto Brun ◽  
Dolores Gonzalez Pacanowska ◽  
Luis M. Ruiz Perez ◽  
Ian H. Gilbert
Keyword(s):  
Trypanosoma Cruzi ◽  
Dihydrofolate Reductase ◽  
Selective Inhibitors ◽  
Design And Synthesis

ChemInform Abstract: The Structure-Based Design and Synthesis of Selective Inhibitors of Trypanosoma Cruzi Dihydrofolate Reductase.

ChemInform ◽  
2010 ◽  
Vol 30 (37) ◽  
pp. no-no
Author(s):  
Fabio Zuccotto ◽  
Reto Brun ◽  
Dolores Gonzalez Pacanowska ◽  
Luis M. Ruiz Perez ◽  
Ian H. Gilbert
Keyword(s):  
Trypanosoma Cruzi ◽  
Dihydrofolate Reductase ◽  
Selective Inhibitors ◽  
Design And Synthesis

scholarly journals Lipophilic Antifolate Trimetrexate Is a Potent Inhibitor of Trypanosoma cruzi: Prospect for Chemotherapy of Chagas' Disease

2005 ◽  
Vol 49 (8) ◽  
pp. 3234-3238 ◽  
Author(s):  
Olga Senkovich ◽  
Vandanajay Bhatia ◽  
Nisha Garg ◽  
Debasish Chattopadhyay
Keyword(s):  
Trypanosoma Cruzi ◽  
Chagas Disease ◽  
Dihydrofolate Reductase ◽  
Drug Target ◽  
Potent Inhibitor ◽  
Pneumocystis Carinii ◽  
Lethal Dose ◽  
Public Health Problem ◽  
Protozoan Parasite ◽  
Track Record

ABSTRACT Trypanosoma cruzi, a protozoan parasite, is the causative agent for Chagas' disease, which poses serious public health problem in Latin America. The two drugs available for the treatment of this disease are effective only against recent infections and are toxic. Dihydrofolate reductase (DHFR) has a proven track record as a drug target. The lipophilic antifolate trimetrexate (TMQ), which is an FDA-approved drug for the treatment of Pneumocystis carinii infection in AIDS patients, is a potent inhibitor of T. cruzi DHFR activity, with an inhibitory constant of 6.6 nM. The compound is also highly effective in killing T. cruzi parasites. The 50 and 90% lethal dose values against the trypomastigote are 19 and 36 nM, and the corresponding values for the amastigote form are 26 and 72 nM, respectively. However, as TMQ is also a good inhibitor of human DHFR, further improvement of the selectivity of this drug would be preferable. Identification of a novel antifolate selective against T. cruzi would open up new therapeutic avenues for treatment of Chagas' disease.

scholarly journals Cloning and expression of the dihydrofolate reductase-thymidylate synthase gene from Trypanosoma cruzi

1994 ◽  
Vol 65 (2) ◽  
pp. 247-258 ◽  
Author(s):  
Pedro Reche ◽  
Rosalia Arrebola ◽  
Asunción Olmo ◽  
Daniel V. Santi ◽  
Dolores Gonzalez-Pacanowska ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Dihydrofolate Reductase ◽  
Thymidylate Synthase ◽  
Cloning And Expression

scholarly journals Expression and characterization of the Trypanosoma cruzi dihydrofolate reductase domain

1996 ◽  
Vol 76 (1-2) ◽  
pp. 175-185 ◽  
Author(s):  
Pedro Reche ◽  
Rosalia Arrebola ◽  
Daniel V. Santi ◽  
Dolores Gonzalez-Pacanowska ◽  
Luis M. Ruiz-Perez
Keyword(s):  
Trypanosoma Cruzi ◽  
Dihydrofolate Reductase ◽  
Reductase Domain

Novel inhibitors of Trypanosoma cruzi dihydrofolate reductase

2001 ◽  
Vol 36 (5) ◽  
pp. 395-405 ◽  
Author(s):  
Fabio Zuccotto ◽  
Marketa Zvelebil ◽  
Reto Brun ◽  
Shafinaz F Chowdhury ◽  
Raffaella Di Lucrezia ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Dihydrofolate Reductase

Synthesis and characterization of potent inhibitors of Trypanosoma cruzi dihydrofolate reductase

2010 ◽  
Vol 18 (11) ◽  
pp. 4056-4066 ◽  
Author(s):  
Norbert Schormann ◽  
Sadanandan E. Velu ◽  
Srinivasan Murugesan ◽  
Olga Senkovich ◽  
Kiera Walker ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Dihydrofolate Reductase ◽  
Synthesis And Characterization

High-resolution gold labeling

1993 ◽  
Vol 51 ◽  
pp. 330-331
Author(s):  
James F. Hainfeld ◽  
Frederic R. Furuya ◽  
Kyra Carbone ◽  
Martha Simon ◽  
Beth Lin ◽  
...  
Keyword(s):  
Dihydrofolate Reductase ◽  
Polypeptide Chain ◽  
External Surface ◽  
Gold Cluster ◽  
Macromolecular Complex ◽  
Gold Compound ◽  
Central Cavity ◽  
Chain Folding ◽  
E Coli ◽  
Chaperonin Groel

A recently developed 1.4 nm gold cluster has been found to be useful in labeling macromolecular sites to 1-3 nm resolution. The gold compound is organically derivatized to contain a monofunctional arm for covalent linking to biomolecules. This may be used to mark a specific site on a structure, or to first label a component and then reassemble a multicomponent macromolecular complex. Two examples are given here: the chaperonin groEL and ribosomes.Chaperonins are essential oligomeric complexes that mediate nascent polypeptide chain folding to produce active proteins. The E. coli chaperonin, groEL, has two stacked rings with a central hole ∽6 nm in diameter. The protein dihydrofolate reductase (DHFR) is a small protein that has been used in chain folding experiments, and serves as a model substrate for groEL. By labeling the DHFR with gold, its position with respect to the groEL complex can be followed. In particular, it was sought to determine if DHFR refolds on the external surface of the groEL complex, or whether it interacts in the central cavity.

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