Chem Core

PROJECT SUMMARY – CHEM CORE The primary goals of the Center of Biomedical Research Excellence (COBRE) for Translational Chemical Biology (CTCB) are to support junior faculty recruitment and mentorship, mission-critical research cores, and growth of an innovative and broad-reaching interdisciplinary translational chemical biology research community. The Center’s theme intersects chemical biology, molecular pharmacology, and pharmaceutical science. CTCB is unique to, and synergistic with, the University of Kentucky’s (UK’s) biomedical research enterprise that offers a wealth of innovative models and potential new drug targets linked to Appalachian Kentucky health disparities. As such, the Center provides a new unifying framework for faculty to create, leverage, and advance novel chemical probes for the study and control of diverse disease-relevant biology. Within this context, the CTCB Chem Core is one of two independent Phase 2 research support cores, that in conjunction with the CTCB Bio Core, operate as an integrated unit to strategically support probe and project development. As the only synthetic chemistry core at UK, the Chem Core will provide infrastructure and expertise to enable computational ligand design, medicinal chemistry, strategic scale-up chemistries, and probe-based target identification and imaging. As new Phase 2 Chem Core resources, the Core will further grow and leverage its exclusive Natural Products Repository and develop new computational platforms for virtual screening and de novo ligand design. In early Phase 2, the Chem Core will support probe optimization and medicinal chemistry of hits identified by the Bio Core for CadA and Tlp3 (Project 7, Alam), quorum-sensing (QS), autoinducer-2 (AI-2) signaling (Project 9, Helmy), and PAC1 receptor (Ignite Scholar, Jaramillo). The Chem Core will also advance bile acid (Project 8, Czuba) and veraguamide (Ignite Scholar, Tidgewell) structure-activity-relationship (SAR) studies. In addition, the Core will leverage new computational methods for de novo CadA and Tlp3 inhibitor design (Project 7) and facilitate new conjugation and click chemistries for human apical sodium-dependent bile acid transporter (ASBT) assay development (Project 8). Continuing rigorous Chem Core tracking and evaluation by the Administrative Core in Phase 2 will ensure efficient Core responsiveness and exemplary services and establish a quantitative cost basis for prospective Chem Core user fees for long-term core sustainability.