Science Concentrates

Kink in the chain

While screening for molecules that affect the cell cycle of frog eggs, researchers stumbled upon ubistatin A, a small molecule that inhibits one of most important degradation pathways in the cell [Science, 306, 117 (2004)]. When a protein has outlived its usefulness, a ligase enzyme tacks on a characteristic chain of ubiquitin molecules. This chain is a red flag to the cell's garbage truck--a cylindrical macromolecular assembly called the proteasome. Ubistatin A (shown) binds to the ubiquitin chain and prevents the proteasome from recognizing the tagged protein, says Randall W. King of Harvard Medical School. Besides their usefulness as biochemical probes, ubistatins point to the ubiquitin chain as a new drug target. Other proteasome inhibitors, under investigation for treating cancer or inflammation, gum up the proteasome's active center.

Protein senses the color of light

The light-absorbing pigment found in a bacterial-membrane-embedded protein interconverts between a cis and a trans form in response to different colors of light, according to a new crystallographic study. John L. Spudich of the University of Texas Medical School, Houston, and Hartmut Luecke of the University of California, Irvine, studied a cyanobacterial rhodopsin protein that contains a lysine-tethered pigment called retinal. They show that under blue light, the all-trans form of the pigment (shown) predominates. But orange light rapidly isomerizes the pigment (at the bond highlighted in red) to cis [Science, published online Oct. 30, http://dx.doi.org/10.1126/ science.1103943]. Cyanobacteria use different chromophores in their photosynthetic light-harvesting complexes depending on the color of available light. The rhodopsin pigment's ability to sense the color of light and pass along that information via protein-protein interactions may control which of these chromophores is produced, they suggest.

DNA reveals new reactions

In addition to directing known reactions, DNA-templated synthesis can lead the way to new reactions, according to a new report. Using this method, David R. Liu and coworkers at Harvard University discovered a previously unknown reaction in which an alkene and alkyne are oxidatively coupled to form an enone in the presence of a palladium catalyst [Nature, 431, 545 (2004)]. The scientists set up the system by attaching reactants to the ends of DNA strands containing a "coding region" to identify the reactant and an "annealing region" to bind to the DNA strand for other reactants. Two pools of these DNA strands are mixed together and allowed to react in the presence of a metal catalyst. The DNA sequences encoding reactants that successfully form bonds are fished out of the mixture, amplified, and hybridized to a DNA microarray. The spots on the array containing the bond-forming substrate combinations fluoresce green, allowing the identification of reactive pairs of substrates out of hundreds of possible combinations.

Sugar-decked polymer detects pathogens

A method to detect pathogenic bacteria by binding to a fluorescent polymer elaborated with pendant sugars that the bacteria recognize during infection has been demonstrated with a carbohydrate-functionalized poly(p-phenylene ethynylene). For example, a mannose-functionalized polymer discriminates between a mannose-binding strain of Escherichia coli and a mutant that does not bind mannose, according to recent work by Peter H. Seeberger at the Swiss Federal Institute of Technology, Zurich, and Timothy M. Swager at MIT [J. Am. Chem. Soc., published online Sept. 25, http://dx.doi.org/10.1021.ja047936i]. Only the mannose-binding strain forms fluorescent clusters after incubation with the polymer. Inasmuch as the specific carbohydrates bound by particular bacteria are known, polymers can be constructed to selectively detect specific pathogens. For carbohydrates that are recognized by several species, a unique fingerprint for a species can be created from its pattern of reactivity with a series of carbohydrate-polymer combinations presented in an array format.

Organometallic catalysts are enzyme-like

Researchers have discovered organometallic catalysts that work about as well as enzymes in anti-Markovnikov hydrations of terminal alkynes to aldehydes. In such hydrations, a carbonyl oxygen is added to the alkyne's terminal carbon, producing an aldehyde, whereas Markovnikov hydrations yield ketones. Alkyne hydrations are generally carried out with strongly acidic or metal-containing catalysts under acidic conditions, but such reactions generally proceed in a Markovnikov manner and produce mostly ketones. Douglas B. Grotjahn and Daniel A. Lev of San Diego State University have now identified organometallic compounds (shown, where X is an anion like PF₆^–) that catalyze anti-Markovnikov alkyne hydrations with extraordinary speed and selectivity [J. Am. Chem. Soc., 126, 12232 (2004)]. The catalysts accelerate aldehyde formation at rates 10 to 11 orders of magnitude faster than those of corresponding uncatalyzed reactions, and they are selective for production of aldehydes over ketones by factors of 10,000-to-1 or more.