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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.
Biological membranes are two-dimensional mixtures of an enormous number of different components. Modeling cell membranes as simple bilayer mixtures reveals rich phase behavior, but how can we use the observed phase behavior to understand the real membranes?
Physical chemistry explains the principles of self-organization of lipids into bilayers that form the matrix of biological membranes, and continuum theory of membrane energetics is successful in explaining many biological processes. With increasing sophistication of investigative tools, there is now a growing appreciation for lipid diversity and for the role of individual lipids and specific lipid-protein interactions in membrane structure and function.
Bioinorganic chemistry remains a vibrant discipline at the interface of chemistry and the biological sciences. Metal ions function in numerous metalloenzymes, are incorporated into pharmaceuticals and imaging agents, and inspire the synthesis of catalysts used to achieve many chemical transformations.
Chemical biology graduate programs that are jointly organized by chemistry and life science departments can offer a stimulating 'bicultural' training environment for students from diverse backgrounds. However, communication, flexibility and responsiveness are crucial for effectively structuring such programs.
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.
