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Science Concentrates Landing Page

September 6, 2004 | A version of this story appeared in Volume 82, Issue 36

Flipping the apoptosis switch

Cancer cells manage to proliferate by evading the apoptosis, or programmed cell death, pathway. Two new studies describe molecules that help turn that pathway back on. In one study, Stanley J. Korsmeyer of the Dana Farber Cancer Institute, Gregory L. Verdine of Harvard University, and coworkers use a hydrocarbon bridge to stabilize a helical peptide that interacts with a protein in the apoptotic pathway [Science, 305, 1466 (2004)]. They use ,-disubstituted nonnatural amino acids with olefin tethers to create the "hydrocarbon staple" by ruthenium-catalyzed olefin metathesis. The stapled peptide induces apoptosis in human leukemia cells transplanted in mice. In the second study, Patrick G. Harran, Xiaodong Wang, Jef K. De Brabander, and coworkers at the University of Texas Southwestern Medical Center, Dallas, describe a small-molecule mimic of a protein that activates cysteine proteases involved in apoptosis [Science, 305, 1471 (2004)]. The molecule (shown) induces apoptosis in human brain cancer and cervical cancer cell cultures.


Enzyme removes methyl groups

An enzyme that removes methyl groups from histones--the scaffolding proteins on which genomic DNA is wrapped for storage--has finally been identified. Chemical modifications made to histones regulate gene expression by controlling access to DNA. Pairs of opposing enzymes control the level of histone phosphorylation and acetylation. Although enzymes that transfer methyl groups to histone lysine and arginine side chains have been identified, enzymes that remove these methyl groups remain unknown. Now, a team led by C. David Allis of Rockefeller University and Scott A. Coonrod of Cornell University's Weill Medical College report that human peptidylarginine deiminase 4 converts methylarginine into citrulline, releasing methylamine (shown) [Science, published online Sept. 2,]. They show that the enzyme removes methylamines from histones both in vitro and in vivo, regulating both histone methylarginine levels and gene transcription. The observations support the long-held suspicion that histone methylation is reversible.


Polymers from oranges and CO2

Aliphatic polycarbonates made from CO2 and epoxides have promise as biodegradable polymeric materials. Although CO2 is an inexpensive feedstock, and its use on a large scale could help control atmospheric emissions, most industrial uses of epoxides involve ethylene oxide, propylene oxide, or cyclohexene oxide derived from petroleum. Geoffrey W. Coates and coworkers at Cornell University have now devised a polycarbonate synthesis that uses limonene oxide derived from citrus fruit as a starting material [J. Am. Chem. Soc., published online Aug. 24,]. Limonene's (R)-enantiomer makes up more than 90% of citrus peel oil. The oxide is commercially available at low cost and is structurally similar to cyclohexene oxide, they point out. The researchers reacted limonene oxide and CO2 under a variety of conditions using -diiminate zinc catalysts. The regiochemistry can be controlled by the reaction temperature to give the trans copolymer (shown) with nearly 99% selectivity.


Nanotube fibers on a large scale

Rumpelstiltskin may have been able to spin straw into gold, but scientists at Rice University are performing a feat whose industrial potential is even more dazzling: They are using a conventional spinning technique to produce macroscopic fibers composed solely of highly aligned single-walled carbon nanotubes (SWNTs) [Science, 305, 1447 (2004)]. The production methods used by Richard E. Smalley, Wen-Fang Hwang, and coworkers are similar to those used in making two of the strongest commercial fibers, Kevlar and Zylon. Zylon is the strongest fiber on the market, and pure nanotube fibers promise to be 10 times stronger still, according to the Rice team. The researchers believe they have overcome a major hurdle to industrial production of nanotube fibers by preparing a concentrated dispersion of SWNTs in a superacid. This dispersion is extruded and coagulated in a controlled manner to produce continuous lengths of highly pure nanotube fibers.


Cradle for newborn protein

The crystal structure of a bacterial chaperone protein, crouched on top of the ribosomal surface, makes clear how the chaperone does its job [Nature, published online Aug. 29,]. "Trigger factor" protects a growing peptide chain from folding incorrectly by creating a hydrophobic protective cage--a cradle--over the ribosomal exit tunnel. Lars Ferbitz and Nenad Ban of ETH Zürich and coworkers did not expect that such a small protein would be able to form a shielded space large enough to allow folding of a protein domain. Ferbitz describes how trigger factor is shaped like a crouching dragon: The N-terminal tail interacts with the ribosome, while the back, head, and C-terminal arms hunch over the exit tunnel. This shields the new protein from cytosolic proteins and allows it to grow large enough to begin to fold correctly on its own.


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