Volume 2 Issue 6, June 2006

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.

The field of chemical biology is now hitting its stride. Chemical biologists have developed essential tools that are being used to illuminate complex cellular events. The application of chemical principles to biological phenomena has revealed new opportunities for drug discovery. This report highlights recent progress and exciting new directions in chemical genetics and drug discovery.

From research contributions in understanding the molecular details of enzyme catalysis to involvement in education and university administration, Jeremy Knowles offers a broad perspective on chemistry and chemical biology.

Identifying the structures of transient intermediates is an essential step in the elucidation of an enzymatic reaction mechanism. Cryocrystallography reveals the structures of three thiamine diphosphate derivatives as intermediates in the action of pyruvate oxidase.

When introduced into living cells, drugs frequently evoke unanticipated responses that are due either to off-target effects or to previously unknown interactions between the intended target and other biochemical pathways. The development of a panel of high-resolution sentinel assays for signal-transduction cascades in human cells promises to enhance the power of chemical genetics and increase the efficiency of drug-discovery research.

In diseases linked to protein aggregation, the initiation of aggregation can be a critical point in the disease mechanism. New studies in cells expressing huntingtin exon I suggest that the initiation of polyglutamine aggregation proceeds by a simple nucleation mechanism.

Because of their transmembrane nature, ion channels are notoriously difficult subjects for high-throughput screening approaches. A new method has been developed that provides a simple, elegant and rapid means for assaying channel function.

Human C-reactive protein (CRP) has been implicated in the inflammatory responses associated with heart attacks and strokes. A small-molecule inhibitor of CRP limits myocardial infarction in rats and should facilitate mechanistic studies of cardiovascular disease.

The June 2006 issue represents one year of Nature Chemical Biology. To mark our anniversary, we have compiled some highlights from our first 12 issues. These free items reflect the editorial scope and the diversity of content featured in Nature Chemical Biology. We hope that you will enjoy them and look forward, with us, to our second year of publication of research at the interface of chemistry and biology.