The Role of Organic Synthesis in Drug Discovery
Angela N. Koehler, Broad Institute of Harvard and MIT
Synthetic organic chemistry continues to play a central role in the discovery and development of therapeutic agents and diagnostic tools. A key challenge for chemists in the “post-genome” era is to develop drugs that target an ever-growing list of new proteins associated with disease. Typical pharmaceutical agents are small organic molecules that modulate the functions of protein targets. During this introduction, we will briefly discuss notable examples of small organic molecules that have been used as probes of biological targets and processes or translated into therapeutics using synthetic methods. We will highlight two fruitful strategies used by organic chemists to develop modern methods in synthetic chemistry and advance discovery of biologically active organic molecules. The first approach involves using insights from naturally occurring bioactive small molecules, often referred to as natural products, to develop new molecules with improved properties as drugs or novel activities as probes. The second approach involves synthesizing diverse collections of structurally complex molecules and screening them to identify novel modulators of a wide-ranging set of biological targets and processes. This overview will provide a foundation for the following presentations that will describe (i) the development of versatile synthetic approaches towards unique hybrid structures composed of natural products and (ii) novel synthetic molecules that serve as probes of the fundamental biology underlying eukaryotic gene expression as well as starting points for transcription-based therapeutics.
Suggested Background Reading:
Schreiber, S. L. Organic synthesis toward small-molecule probes and drugs. Proc. Natl. Acad. Sci. USA, 2011 EMBARGOED, not yet in PNAS Early Edition online but this may be available before the symposium as several of the other articles from this special edition are already accessible in Pubmed.