Antibacterial drugs

Fleming's unfinished. Wainwright, M. Perspect. Biol. Med. 45, 529–538 (2002)

Just as music historians complete the unfinished symphonies of composers, Milton Wainwright has pieced together findings from Alexander Fleming's lab books, which could help restore the much-maligned reputation of the discoverer of penicillin. Far from being a lazy researcher who lost interest in his discovery, but was happy to take most of the credit for it becoming a medical breakthrough, Fleming's lab notes reveal that he spent many years meticulously screening airborne moulds for antibiotic properties, and made possibly one of the first observations that bacteria can develop resistance to antibiotics.

Protein folding and disease

Absolute comparison of simulated and experimental protein-folding dynamics. Snow, C. D., Nguyen, H., Pande, V. S. & Gruebele, M. Nature 420, 102–106 (2002)

One reason that it is so difficult to predict the shape (and therefore function) of a protein from its amino-acid sequence using computers is because folding occurs in the order of microseconds in the cell, but it takes an average computer 1 day to simulate only 1 nanosecond of folding. Snow and colleagues used a program called Folding@Home to distribute small portions of the calculations of the folding of an artificial 23-amino-acid mini-protein called BBA5 among the screensavers of 30,000 computers. Secondary structures and the folding rates were all consistent with the available experimental evidence, and the formation of several intermediates confirmed the heterogeneous nature of protein folding.

Adrenoceptor pharmacology

Pharmacological characterization of CGP 12177 at the human β2-adrenoceptor. Baker, J. G., Hall, I. P. & Hill, S. J. Br. J. Pharmacol. 137, 400–408 (2002)

The class of drugs known as beta-blockers, long known for their hypotensive benefits, are increasingly being used for the chronic treatment of congestive heart failure, and also seem to have potential for treating inflammatory airway disease. The mechanism of action of beta-blockers in these newer indications is unclear. Here, Stephen Hill's group present evidence that a well-known, high-affinity 'beta-blocker', CGP 12177, which has already been shown to have agonist activity at the β1-adrenoceptor, also has partial agonist behaviour at the β2-adrenoceptor. This adds weight to the possibility that some of the newly observed effects of this group of drugs might in fact arise from receptor activation, rather than the presumed deactivation.