Biotechnology

Controlling protein activity with ligand-regulated RNA aptamers.Vuyisich, M. & Beal, P. A. Chem. Biol. 9, 907–913 (2002)

Aptamers — single-stranded nucleic acids that can fold into intricate globular structures capable of binding proteins with high potency and specificity — have potential both as therapeutics and as tools to probe cellular processes. Vuyisch and Beal describe a general method for discovering aptamers that bind to a target protein, with this binding being regulable by a small molecule. Such ligand-regulated aptamers offer greater temporal control of the targeted protein activity, and should prove particularly useful in defining the function of proteins that are involved in processes in which the timing of events is crucial, such as the cell cycle.

Inflammatory diseases

The role of prostaglandin E2 receptors in the pathogenesis of rheumatoid arthritis.McCoy, J. M. et al. J. Clin. Invest. 110, 651–658 (2002)

Prostaglandin E2 — which can act through at least four different G-protein-coupled receptors, EP1–EP4 — has been implicated in rheumatoid arthritis. Mice that lack the EP4 receptor show decreased incidence and severity of disease in a model of rheumatoid arthritis, but this is not the case in mice that lack either EP1, EP2 or EP3, indicating that EP4 might represent a novel and specific therapeutic target.

Chemical-library design

Do structurally similar molecules have similar biological activity?Martin, Y. C. et al. J. Med. Chem. 45, 4350–4358 (2002)

When designing diverse combinatorial libraries or selecting diverse compounds to add to a screening library, computational chemists often reject compounds that are too similar (as assessed by a computational calculation) to compounds that are already in the library to save resources. Martin et al. provide data that indicate that the relationship between computational calculations of compound similarity and biological activity is not as strong as has been previously assumed, which has important implications for strategies for compound acquisition and the design of combinatorial libraries.

Anticancer drugs

Medulloblastoma growth inhibition by Hedgehog pathway blockade.Berman, D. M. et al. Science 297, 1559–1561 (2002)

There are no effective treatments for medulloblastoma, the most common malignant brain tumour in children. Using cyclopamine — a known antagonist of a protein involved in the Hedgehog signalling pathway — Berman et al. show that the pathway is important for the growth of medulloblastoma cells and is therefore a potential target for therapeutic intervention.