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Chemical biology is an interdisciplinary field that is undergoing rapid expansion around the globe. Recently, the Japanese Society for Chemical Biology sponsored its inaugural scientific meeting to discuss research at the interface of chemistry and biology.
Sphingosine 1-phosphate (S1P), a lysophospholipid and known immune regulator, stimulates distinct signaling pathways. A specific S1P antagonist that can be used systemically for the first time provides an indispensable tool for elucidating the therapeutic potential of the S1P signaling pathway.
Nitric oxide (NO) regulates a broad range of biological processes, yet many intracellular details of NO-mediated processes remain hidden. A new fluorescein derivative capable of direct detection provides a key advance in determining NO function in vivo.
DNA-binding proteins accomplish the remarkable feat of finding their correct target sequences within a sea of genomic DNA. A new study uses NMR spectroscopy to show the mechanism by which proteins may hop between and slide along DNA as they search for their target binding sites.
Dynamin is a large GTPase that participates in the severing of membrane-bound vesicles. A small-molecule inhibitor specific for the dynamin family of GTPases has been identified and reveals new aspects of membrane dynamics.
Nitrosoperoxycarbonate anion, a reactive species generated in inflammation processes, is able to specifically oxidize guanine bases with a sequence selectivity that is almost opposite from that usually observed for one-electron oxidants.
Copper is a requisite cofactor in myriad cellular enzymes and is shuttled to different cellular sites for the assembly of copper-containing enzymes by Cu(I)-binding metallochaperones. NMR structural studies now reveal a key step in copper ion trafficking to sites of use.
One-bead-one-compound combinatorial peptidomimetic libraries, in conjunction with a high-stringency screening method, are a powerful tool for screening peptide and peptidomimetic ligands for target proteins. Picomolar-affinity peptidomimetics for the integrin α4β1 have now been developed and have been successfully used to image α4β1-expressing tumors in living mice.
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.
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.
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.
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 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.
Translation starts with the assembly of the ribosome from its subunits, which requires the formation of intersubunit bridges. A combinatorial mutagenesis approach has now identified a number of the 16S rRNA residues involved in intersubunit bridging that are functionally important for the ribosome.
