Volume 2 Issue 12, December 2006

By building on the successes of the past and leveraging both innovative technologies and predictive knowledge, scientists can develop smarter ways to create a molecular armamentarium of chemical and biological medicines.

Translational research in academia is extending beyond the traditional involvement in clinical trials to the early phases of the drug discovery process. Examples of successful academic-industrial partnerships illustrate the ways in which they can enable the discovery of new medicines.

Seeking to maintain a supply of effective antibiotics, Stuart Levy combines research in microbiology and antibiotic drug discovery with a strong commitment to public communication.

As head of the Office of Orphan Products Development, Marlene Haffner offers a perspective on the immense influence the Orphan Drug Act has had in promoting research on and awareness of rare diseases.

Fragment-based drug design capitalizes on the modular binding of low-molecular-weight, low-affinity ligands. However, the deconstruction of lead-like inhibitors into putative fragments reveals the surprising complexity of dealing with low-affinity leads, thereby challenging oversimplification of these leads and highlighting the richness of their chemical diversity and molecular recognition.

Chemically synthesizing complex oligosaccharides remains a significant challenge. Through the addition of hydrophobic appendages to 'unnatural' substrates, some oligosaccharide-forming glycosyltransferases can direct the formation of distinct sugar linkages while maintaining stereoselectivity.

Ascidians obtain diverse libraries of cytotoxic compounds by maintaining cyanobacterial symbionts that have combinatorial variants of a natural-product pathway. The biosynthetic flexibility of this route can be used to genetically engineer new substances.

The sheer quantity and complexity of gene expression data can provide extraordinarily accurate descriptions of differences between states of cells, tissues and whole organisms. A compendium of genomic signatures that attempts to describe all biological states has the potential to reveal hidden connections among drugs, genes and diseases.

The development of new therapeutic agents has required the close collaboration of chemists and biologists in identifying drug targets or lead compounds and developing them toward the clinic. This month we include a series of articles that focus on how chemical biologists in academic and industrial settings enhance our understanding of biological systems and advance the next generation of therapeutic agents.