Commentary

The function of many biologically active molecules requires the presence of carbon-nitrogen bonds in strategic positions. The biosynthetic pathways leading to such bonds can be bypassed through chemical synthesis to synthesize natural products more efficiently and also to generate the molecular diversity unavailable in nature.

Eukaryotic cells are specialized, interdependent functional units of complex tissues that are composed of metabolically integrated systems defined by chemically distinct organelles that operate as reaction vessels. It is now clear that the small-molecule and polymer-based composition of these organelles plays a crucial role in generating and maintaining protein folds and functions through the systems chemistry of the local environments.

Iron-sulfur clusters have critical roles in proteins from diverse organisms and in a broad range of biological processes. Recent discoveries raise exciting challenges for future research by bioinorganic chemists and chemical biologists.

Developing small-molecule inhibitors against protein-protein interaction targets is among the most difficult challenges in contemporary drug discovery. Recent developments in our understanding of this problem, and in the knowledge and tools available to address it, give cause for renewed hope, but substantial challenges remain.

The goal of high-throughput screening (HTS) from the perspective of the biologist is to identify a highly specific small molecule that can be used to inhibit a protein in its normal biological context. Although several useful small molecules have been identified with HTS, there are many challenges to be considered when contemplating a screen, especially by those unfamiliar with chemical biology.

Chemical biology has historical roots that date back to the birth of chemistry and biology as distinct sciences.

Chemical insight into biological function is the holy grail of structural biology. Small molecules are central players as building blocks, effectors and probes of macromolecular structure and function.

Chemical biology, broadly defined as the application of chemistry to the study of molecular events in biological systems, presents an opportunity for the reorganization and revitalization of the chemistry curriculum.

The growth of research at the chemistry-biology interface provides a unique opportunity to inspire undergraduate students to pursue careers in science and to educate science and nonscience students broadly in both chemical and biological sciences.

Chemical biologists studying natural-product pathways encoded in genomes have unearthed new chemistry and insights into the evolution of biologically active metabolites.

Small molecules have critical roles at all levels of biological complexity and yet remain orphans of the central dogma. Chemical biologists, working with small molecules, expand our understanding of these central elements of life.