Dr. Bongkoch Tarnchompoo has been awarded the Grand Challenges Explorations (GCE) grant from the Bill & Melinda Gates Foundation. Dr. Bongkoch will attempt to synthesize new dual-mode inhibitors of Plasmodium falciparum dihydrofolate reductase (pfDHFR) which will be tested for antimalarial activities against both pyrimethamine-sensitive and resistant parasites, and the structures of the complexes with both types of pfDHFR will be determined. The award will be in the amount of USD 100,000 for a one year period, starting from May 2009.
Drug resistance of the malaria parasites is one of the most important problems in malaria control. Plasmodium falciparum dihydrofolate reductase (pfDHFR), an essential enzyme in the folate pathway, is validated target for antifolate antimalarials. Resistance to DHFR inhibitors is explained by the occurrence of point mutations in the enzyme. The main goal of malaria research at BIOTEC is the development of new antifolates to overcome antifol resistance. BIOTEC research team has succeeded in the development of new antifolates with lower nanomolar antimalarial activity. The team currently proposes new designs of inhibitors which can automatically modulate their binding modes to suit the catalytic sites which they encounter. The bidentate antifolates which target both the wild-type and mutant DHFRs will be designed based on the known modes of binding to the active site and structural effects of mutations, so that the variant targets can be accessed. The dual-mode binding capacity of inhibitors from these designs should make them effective for any forms of DHFR, and therefore limit the development of resistance through further mutations.
Dr. Bongkoch obtained doctoral degree in Organic Chemistry from the Department of Chemistry at Mahidol University. She has been with BIOTEC since 1993, and is now a member of Protein-Ligand Engineering and Molecular Biology Laboratory.
For more information on Grand Challenges Explorations, please visit at http://www.grandchallenges.org/Explorations/Pages/Introduction.aspx
Posted on 06 May 2009.