Aptamers on the scaffold

In independent reports published in Proc. Natl. Acad. Sci. USA 6, 8567–8572, 1999) and Science (285, 591–595, 1999), two teams of researchers have recently described nearly identical approaches for identifying novel components of cellular signaling pathways, technology that should prove useful both in basic research and the identification of new drug targets. Each group screened yeast cells expressing a library of aptamers—short random peptide sequences expressed on a larger protein scaffold—to identify peptides that inhibit specific intracellular signals in yeast. Once inhibitory peptides had been identified, they were used as "bait" in two-hybrid screens to determine which yeast gene products they were binding. The approach identified new components of the yeast mating pheromone signaling pathway and the mitotic spindle checkpoint. Having proven the concept, the approach could conceivably be employed for signaling studies and drug target identification in mammalian cells, which lack the power of yeast genetics. While emphasizing that several hurdles remain before the technique becomes standard practice, Roger Brent, senior author on the PNAS paper, says that "if the two-hybrid experience is a guide, I would guess this is about a year away from widespread use by relatively unsophisticated laboratories."