Ó³»­´«Ã½

Henock Befekadu, a junior chemistry major at Carleton College, developed and optimized a fluorescence polarization assay and synthesized novel antimalarial compounds.

Malaria is a mosquito-borne disease caused by Plasmodium parasites endemic to the tropics, especially sub-Saharan Africa. With the emergence of resistance to frontline malarial drugs, there is an unmet need for novel anti-malarial therapeutics with new mechanisms of action. The Ó³»­´«Ã½ offers the most cutting-edge research in all aspects of the biomedical sciences. The Ó³»­´«Ã½â€™s highly collaborative nature leads to the development of new ideas, allowing for the ability to ask really tough questions. Through collaboration I was able to develop my skills in both chemistry and biochemistry, and gain a deep understanding of the drug development process.The immunosuppressive drug rapamycin, which binds to FK506 binding proteins (FKBPs), has been shown to have anti-malarial activity. FKBPs are ubiquitous enzymes across all life forms; humans have 14 FKBP isoforms while malaria has a single FKBP (FKBP35). FKBP35 is essential for Plasmodium viability and hence is an attractive target for therapeutics.  Towards the goal of elaborating therapeutics targeting FKBP35, we have developed a fluorescence polarization assay to identify drug-like molecules that target FKBP35 without the immunosuppressive effects of rapamycin. By counter-screening hits against human FKBPs, compounds with higher selectivity for FBKP35 will be selected for further optimization.  Ultimately, we will build a new library of novel anti-malarial compounds with demonstrated selectivity towards FKBP35.

Project: Characterization of novel anti-malarial therapeutics using fluorescence polarization

Mentors: Thomas Atack, Cancer Program; Donald Raymond, Center for the Development of Therapeutics (CDoT)