The ability to build and edit chemical structure is immensely powerful. We are molecule builders seeking to approach challenging problems at the interface of chemistry, biology, and medicine from a molecular perspective. A main focus of our research involves the chemistry and biology of natural products that target protein-protein interaction (PPI) interfaces. The human 'interactome' is comprised of over 300,000 PPIs that maintain cell homeostasis. Because deregulation of these interactions is often involved in disease pathobiology, each PPI can be viewed as a potential therapeutic target. At a more fundamental level, small-molecules that can modulate these interactions, and the downstream pathways they control, also provide valuable tools to disentangle the roles of individual PPIs in regulating biological pathways. Our work in this area focuses on structurally complex secondary metabolites that bind protein-protein contacts in human cell culture. We develop efficient strategies and tactics to prepare these targets. This synthetic chemistry used to guide deep seeded changes to the molecular motif intended to enhance a desired function. Following this blueprint, we are currently working on several fronts to interrogate PPI networks that are beyond the reach of existing small-molecule-based strategies.