XWH - 05 - 2 - 0025 TITLE : Evaluation of Purine Salvage as a Chemotherapeutic Target in the Plasmodium

Structural Determinants of the 5′-Methylthioinosine Specificity of Plasmodium Purine Nucleoside Phosphorylase

Plasmodium parasites rely upon purine salvage for survival. Plasmodium purine nucleoside phosphorylase is part of the streamlined Plasmodium purine salvage pathway that leads to the phosphorylysis of both purines and 5'-methylthiopurines, byproducts of polyamine synthesis. We have explored structural features in Plasmodium falciparum purine nucleoside phosphorylase (PfPNP) that affect efficienc...

The plasma membrane permease PfNT1 is essential for purine salvage in the human malaria parasite Plasmodium falciparum.

The human malaria parasite Plasmodium falciparum relies on the acquisition of host purines for its survival within human erythrocytes. Purine salvage by the parasite requires specialized transporters at the parasite plasma membrane (PPM), but the exact mechanism of purine entry into the infected erythrocyte, and the primary purine source used by the parasite, remain unknown. Here, we report tha...

Malaria parasite type 4 equilibrative nucleoside transporters (ENT4) are purine transporters with distinct substrate specificity.

Malaria, caused by Plasmodia parasites, affects hundreds of millions of people. As purine auxotrophs, Plasmodia use transporters to import host purines for subsequent metabolism by the purine salvage pathway. Thus purine transporters are attractive drug targets. All sequenced Plasmodia genomes encode four ENTs (equilibrative nucleoside transporters). During the pathogenic intraerythrocytic stag...

XWH - 06 - 1 - 0623 TITLE : Nanospheric Chemotherapeutic and Chemoprotective Agents

Evaluation of the Trypanosoma brucei 6-oxopurine salvage pathway as a potential target for drug discovery

Due to toxicity and compliance issues and the emergence of resistance to current medications new drugs for the treatment of Human African Trypanosomiasis are needed. A potential approach to developing novel anti-trypanosomal drugs is by inhibition of the 6-oxopurine salvage pathways which synthesise the nucleoside monophosphates required for DNA/RNA production. This is in view of the fact that ...