Natural Product Synthesis for Drug Discovery and Chemical Biology

Natural products are biosynthesized by protein catalysts, and as such natural-product and protein structures must necessarily have co-evolved to bind to one another selectively. Most macromolecular targets in humans have functional counterparts, possessing sequence similarity, in lower eukaryotes and prokaryotes. As a result, the biological activity of natural products in human cells is a consequence of their co-evolution alongside similar targets within the producing or neighboring organism in the environment. Natural products are central to biology and medicine, serving as pharmaceutical leads, drugs, and powerful reagents for studying cell biology. Chemical biology uses small molecules to study and manipulate biological systems. The great success of natural products in drug discovery comes from their structural diversity. The antibody-drug conjugate is a therapeutic modality consisting of a monoclonal antibody attached to a cytotoxic, small-molecule payload through a linker.