ABSTRACT
The testing of small, synthetic organic molecules for their ability to modify the biological activity of enzymes, receptor, etc., for use as human therapeutics is the process typically referred to as drug discovery. This process has evolved significantly over the last several decades with the advent of increasingly sophisticated biological and chemical methodologies, as well as laboratory scale automation. In the first half of the twentieth century, drug discovery was primarily performed by chemists and pharmacologists. The pharmacologist’s tool of choice was in vivo bioassays to test mixtures of compounds isolated from natural product sources by natural product chemists or small organic compounds that had been synthesized individually by organic chemists. The realization that protein-protein and protein-small molecule interactions transmitted information in cellular biochemical pathways was the seminal observation that led to the ‘‘lock-and-key’’ hypothesis of biomolecular interactions. This concept that the interaction of specific shapes, charges, etc., on biological molecules can serve to control cellular and organism metabolism is now well
established. The discovery of small organic molecules that antagonize or agonize biochemical interactions relevant to disease processes is the goal of scientists engaged in modern drug discovery. Further advances in protein purification and structural analysis has led to an even greater understanding of these molecular recognition elements which, along with advances in computer-aided design software/hardware, has lead to the development of rational design of small organic molecules for synthesis and testing.
