The National Institute of Allergy and Infectious Diseases (NIAID) awarded a $170,000 Project Grant under the Allergy and Infectious Diseases Research program (CFDA 93.855) to Prokaryotics Incorporated, a biotechnology company focused on developing novel antibiotics. The funding will support structure-based design of antifungal inhibitors targeting the glycosylphosphatidylinositol (GPI) ethanolamine phosphate transferase, MCD4, to address the critical need for new antifungal agents with novel mechanisms of action. The 2-year project aims to perform cryo-EM structural studies of the C. albicans MCD4 enzyme and its human ortholog to guide the synthesis and evaluation of up to 30 novel semi-synthetic antifungal analogs. The goal is to identify analogs with improved antifungal potency and selectivity compared to the lead compound, M743, which also inhibits GPI biosynthesis.