Drug Discovery

Three-hybrid for mammalian cells

As an extension of the yeast two-hybrid systems for detecting protein-protein interactions, yeast three-hybrid systems are used to screen for proteins that interact with a small molecule or vice versa. For drug discovery, however, it would be advantageous to perform these types of screens in mammalian cells. Caligiuri et al. now describe MASPIT, or mammalian small molecule–protein interaction trap, a mammalian three-hybrid system.

Caligiuri, M. et al. Chem. Biol. 13, 711–722 (2006).

Chemical Biology

A new tag-probe system for labeling proteins

Short peptide tag–fluorescent small molecule pairs such as the tetracysteine motif–FlAsH dye are indispensable for cell-biology applications. Ojida et al. report that an oligo-aspartate tag and a fluorescently labeled multinuclear zinc(II) complex can serve as a new system for labeling cell-surface proteins. Notably, the properties of the probe can be easily tuned to suit the application.

Ojida, A. et al. J. Am. Chem. Soc. 128, 10452–10459 (2006).

Cell Biology

Multiplex measurements of neuronal signaling

Signal propagation through individual neurons is often studied using electrophysiology techniques. Patolsky et al. have now designed a cell culture–compatible field-effect transistor array of silicon nanowire for the multiplex arraying of neurons. This array facilitates highly sensitive, spatially resolved detection of neuronal signaling, with potential applications in drug discovery and testing.

Patolsky, F. et al. Science 313, 1100–1104 (2006).

Proteomics

Measuring the half-lives of proteins

Using a TAP-tagged yeast library and western blotting after inhibition of protein synthesis, Belle et al. have measured the half-lives of more than 3750 proteins in the yeast proteome. This was the final piece of the puzzle that has now allowed them to construct a quantitative model of protein metabolism, using previous large-scale measurements of mRNA levels, translation rates and protein abundances.

Belle, A. et al. Proc. Natl. Acad. Sci. USA 103, 13004–13009 (2006).

Imaging and visualization

Quadruplex molecular beacons

The hairpin-shaped molecular beacons are becoming increasingly important tools for highly sensitive and specific DNA and RNA detection. When closed, the fluorophore on one end of the molecular beacon is quenched by the quencher at the other end. When bound to a target sequence, however, the hairpin opens and fluorescence is restored. Bourdoncle et al. now demonstrate that molecular beacons employing a G-quadruplex motif can be constructed, which may give the user more control over their thermodynamic and kinetic properties.

Bourdoncle, A. et al. J. Am. Chem. Soc. 128, 11094–11105 (2006).