Kinetics mechanism and regulation of native human hepatic thymidine phosphorylase.

Thymidine phosphorylase (TP; EC 2.4.2.

Enzymes of pyrimidine salvage pathways in intraerythrocytic Plasmodium falciparum.

Malaria remains a significant public health problem worldwide with an estimated annual global incidence of 200 million and an estimated 450,000 annual deaths. Among the five known human malarial species, Plasmodium falciparum is the deadliest and most resistant to antimalarials. Hence, there is a need for new antimalarial targets.

Distinct substrate specificity and physicochemical characterization of native human hepatic thymidine phosphorylase.

Thymidine phosphorylase (TP; EC 2.4.2.

Pyrimidine metabolism in schistosomes: A comparison with other parasites and the search for potential chemotherapeutic targets.

Schistosomes are responsible for the parasitic disease schistosomiasis, an acute and chronic parasitic ailment that affects >240 million people in 70 countries worldwide. It is the second most devastating parasitic disease after malaria. At least 200,000 deaths per year are associated with the disease.

Kinetic mechanism of Toxoplasma gondii adenosine kinase and the highly efficient utilization of adenosine.

Initial velocity and product inhibition studies of Toxoplasma gondii adenosine kinase (TgAK, EC 2.7.1.

Isolation and substrate specificity of an adenine nucleoside phosphorylase from adult Schistosoma mansoni.

An adenine nucleoside phosphorylase (ANP, EC none) activity was identified and partially purified from extracts of Schistosoma mansoni by chromatofocussing column chromatography and molecular sieving. The enzyme is distinct from purine nucleoside phosphorylase (PNP, EC 2.4.

Nucleoside kinases in adult Schistosoma mansoni: phosphorylation of pyrimidine nucleosides.

Competition studies and column chromatography demonstrated that adults Schistosoma mansoni contains three nucleoside kinases that can phosphorylate pyrimidine nucleosides; a non-specific deoxyriboside kinase (EC 2.7.1.

Effect of mimetic CDK9 inhibitors on HIV-1-activated transcription.

Potent anti-retroviral therapy has transformed HIV-1 infection into a chronic manageable disease; however, drug resistance remains a common problem that limits the effectiveness and clinical benefits of this type of treatment. The discovery of viral reservoirs in the body, in which HIV-1 may persist, has helped to explain why therapeutic eradication of HIV-1 has proved so difficult. In the current study, we utilized a combination of structure-based analysis of cyclin/CDK complexes with our previously published Tat peptide derivatives.

Potent combination therapy for human breast tumors with high doses of 5-fluorouracil: remission and lack of host toxicity.

Purpose: The purpose of this investigation was to evaluate the effectiveness of oral 5-(phenylthio)acyclouridine (PTAU) in reducing 5-fluorouracil (FUra) host toxicity and enhancing its chemotherapeutic efficacy against human breast tumors. PTAU is a potent and specific inhibitor of uridine phosphorylase (UP, EC 2.4.

Paracrine stimulation of endothelial cell motility and angiogenesis by platelet-derived deoxyribose-1-phosphate.

Objective: Micromolar concentrations of the proangiogenic metabolite deoxyribose-1-phosphate (dRP) were detected in platelet supernatants by mass spectrometry. In this study, we assessed whether the release of dRP by platelets stimulates endothelial cell migration and angiogenesis.

Methods And Results: Protein-free supernatants from thrombin-stimulated platelets increased human umbilical vein endothelial cell migratory activity in transmigration and monolayer repair assays.

Carbocyclic 6-benzylthioinosine analogues as subversive substrates of Toxoplasma gondii adenosine kinase: biological activities and selective toxicities.

Toxoplasma gondii adenosine kinase (EC 2.7.1.

Structure-activity relationships of carbocyclic 6-benzylthioinosine analogues as subversive substrates of Toxoplasma gondii adenosine kinase.

Carbocyclic 6-benzylthioinosine analogues were synthesized and evaluated for their binding affinity against Toxoplasma gondii adenosine kinase [EC.2.7.

7-Deaza-6-benzylthioinosine analogues as subversive substrate of Toxoplasma gondii adenosine kinase: activities and selective toxicities.

Toxoplasma gondii adenosine kinase (EC.2.7.

Structure-activity relationships of 7-deaza-6-benzylthioinosine analogues as ligands of Toxoplasma gondii adenosine kinase.

Several 7-deaza-6-benzylthioinosine analogues with varied substituents on aromatic ring were synthesized and evaluated against Toxoplasma gondii adenosine kinase (EC.2.7.

Uridine protects cortical neurons from glucose deprivation-induced death: possible role of uridine phosphorylase.

We previously reported that uridine blocked glucose deprivation-induced death of immunostimulated astrocytes by preserving ATP levels. Uridine phosphorylase (UPase), an enzyme catalyzing the reversible phosphorylation of uridine, was involved in this effect. Here, we tried to expand our previous findings by investigating the uridine effect on the brain and neurons using in vivo and in vitro ischemic injury models.

Suppression of thymidine phosphorylase expression by promoter methylation in human cancer cells lacking enzyme activity.

Purpose: Thymidine phosphorylase (TP, EC 2.4.2.

Adenosine metabolism in Toxoplasma gondii: potential targets for chemotherapy.

Toxoplasma gondii is an intracellular parasitic protozoan that infects approximately a billion people worldwide. Infection with T. gondii represents a major health problem for immunocompromised individuals, such as AIDS patients, organ transplant recipients, and the unborn children of infected mothers.

Synthesis, biological evaluation and molecular modeling studies of N6-benzyladenosine analogues as potential anti-toxoplasma agents.

Toxoplasma gondii is an opportunistic pathogen responsible for toxoplasmosis. T. gondii is a purine auxotroph incapable of de novo purine biosynthesis and depends on salvage pathways for its purine requirements.

Substrate analogs induce an intermediate conformational change in Toxoplasma gondii adenosine kinase.

Adenosine kinase (AK) is a key enzyme in purine metabolism in the ubiquitous intracellular parasite Toxoplasma gondii and is a potential chemotherapeutic target for the treatment of T. gondii infections. To better understand the structure-activity relationship of 6-substituted purine ribosides, the structures of the T.

Uridine prevents the glucose deprivation-induced death of immunostimulated astrocytes via the action of uridine phosphorylase.

We previously reported that in immunostimulated astrocytes, glucose deprivation induced cell death via the loss of ATP, reduced glutathione, and mitochondrial transmembrane potential. The cytotoxicity was due to reactive nitrogen and oxygen species and blocked by adenosine, a purine nucleoside, via the preservation of cellular ATP. Here, we investigated whether uridine, a pyrimidine nucleoside, could prevent the glucose deprivation-induced cytotoxicity in LPS+IFN-gamma-treated (immunostimulated) astrocytes.

Modulation of 5-fluorouracil host-toxicity and chemotherapeutic efficacy against human colon tumors by 5-(Phenylthio)acyclouridine, a uridine phosphorylase inhibitor.

Purpose: The purpose of this investigation was to evaluate the effectiveness of oral 5-(phenylthio)acyclouridine (PTAU) in reducing 5-fluorouracil (FUra) host-toxicity and enhancing its chemotherapeutic efficacy against human colon tumors. PTAU is a potent and specific inhibitor of uridine phosphorylase (UrdPase, EC 2.4.

Structure of Toxoplasma gondii adenosine kinase in complex with an ATP analog at 1.1 angstroms resolution.

The obligate intracellular parasite Toxoplasma gondii is incapable of synthesizing purine nucleotides de novo and relies completely on purines salvaged from the host cells. Adenosine is the preferred precursor and is phosphorylated by adenosine kinase (AK), the most active enzyme in adenosine metabolism in T. gondii.

6-Benzylthioinosine analogues: promising anti-toxoplasmic agents as inhibitors of the mammalian nucleoside transporter ENT1 (es).

Certain 6-benzylthioinosine analogues have been identified as potential chemotherapeutic agents against Toxoplasma gondii in cell culture and animal models. These compounds are selectively transported and metabolized by toxoplasma infected, but not uninfected, cells. In sharp contrast to mammalian nucleoside transporters, the toxoplasma adenosine/purine transporter (TgAT) allows the transport of these 6-benzylthioinosine analogues into infected cells.

Structural basis for inhibition of Escherichia coli uridine phosphorylase by 5-substituted acyclouridines.

Uridine phosphorylase (UP) catalyzes the reversible phosphorolysis of uridine to uracil and ribose 1-phosphate and is a key enzyme in the pyrimidine-salvage pathway. Escherichia coli UP is structurally homologous to E. coli purine nucleoside phosphorylase and other members of the type I family of nucleoside phosphorylases.

6-Benzylthioinosine analogues as subversive substrate of Toxoplasma gondii adenosine kinase: activities and selective toxicities.

Toxoplasma gondii adenosine kinase (EC.2.7.