The power of chemical synthesis

Chemical synthesis provides access to molecules that are unavailable from nature, offering tools to interrogate, perturb, and control biological processes. In this arena, probes for endogenous metabolites present a unique challenge, operating at the knife’s edge of fidelity and functionality. The need for precision is particularly acute with cholesterol metabolites like 20(S)-hydroxycholesterol, where a single stereocenter can mean the difference between the creation and the destruction of a human embryo. To understand how nature leverages atomic structure to coordinate biological systems, our lab is assembling a library of structurally precise, functionalized probes for comprehensive analysis of cholesterol metabolite signaling. In the context of this work, we are designing biorthogonal functional groups for target protein capture and modification and developing new methods for mild, efficient synthesis of structurally complex probe molecules.