Discipline: Chemistry and Chemical Sciences
Subcategory: Biochemistry (not Cell and Molecular Biology and Genetics)
Room: Exhibit Hall A
Henock B. Befekadu - Carleton College
Co-Author(s): Thomas C. Atack, Broad Institute, Cambridge, MA; Donald D. Raymond, Broad Institute, Cambridge, MA; William R. Sellers, Broad Institute, Cambridge, MA
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 immunosuppressive drug rapamycin, which binds to FK506 binding proteins (FKBPs), has been shown to have anti-malarial activity. FKBPs are ubiquitous enzymes across all lifeforms, 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 targets 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.
Funder Acknowledgement(s): NHGRI R25 DAP; Sellers Starting Fund
Faculty Advisor: Thomas C. Atack, email@example.com
Role: I developed a fluorescence polarization assay in order to test the relative drug potency of all the drugs in a small library of compounds that I synthesized.