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Discovery of protein-metabolite and protein-substrate interactions that can specifically regulate genes involved in human biology is an important pursuit, as the study of such interactions can expand our understanding of human physiology and reveal novel therapeutic targets. The identification and characterization of these interactions can be approached from different perspectives. Chemists often use bioactive small molecules, such as natural products or synthetic compounds, as probes to identify therapeutically relevant protein targets. Biochemists and biologists often begin with a specific protein and seek to identify the endogenous ligands that bind to it. These interests have led to the development of methodology that relies heavily on synthetic and analytical chemistry to identify interactions, an approach that is complemented by in vivo strategies for validating the biological consequences of specific interactions.