Chapter 9 - Biology Oriented Synthesis and Diversity Oriented Synthesis in Compound Collection Development

Abstract

Progress in the biological sciences during the last decades has led to a steep increase in knowledge about basic biological processes as well as the factors leading to their misregulation and ultimately the establishment of disease. This data provides the basis for identifying interaction points by a chemical-biological approach and offers new opportunities for the development of therapies. This chapter addresses two complimentary approaches to compound collection development, namely, Diversity Oriented Synthesis (DOS) and Biology Oriented Synthesis (BIOS). Screening of DOS libraries has yielded important new biological probes, which have increased the understanding of various biological processes. Combinatorial chemistry involving DOS principles is a useful method for generating compounds with significant potential in chemical biology and medicinal chemistry research. More importantly, DOS combined with phenotype-based screening has emerged as a powerful tool to study biological systems and has led to the discovery of new bioactive molecules. The increasing number of biological targets being identified in the postgenomic era will also accelerate drug discovery in academia and the pharmaceutical industry. Whereas DOS takes into consideration the structural aspects of the small molecule world, BIOS revolves around a common axis in the evolution of the worlds of proteins and small molecules and tries to analyze and explore their natural interfaces. The exciting potential of the two complementary approaches (DOS and BIOS) to facilitate advances in chemical biology research and drug discovery will be realized to a greater extent in the coming years as the scientific community continues to explore the interactions between chemistry and biology.