10WWW.CEN-ONLINE.ORG MARCH 30, 2009

WHEN CANCERS STOP responding to chemotherapy, one of the culprits is a protein transporter that expels drugs

out of diseased cells, thereby preventing the benefits of treatment. Now researchers are

reporting the first mammalian X-ray crystal structure of this transporter, P-glycopro-tein. The work provides a first step toward

the design of drugs to thwart its action.Human P-glycoprotein is often referred to

as a “hydrophobic vacuum cleaner” be-cause the membrane protein sucks up

all sorts of greasy molecules—includ-ing beneficial drugs—that make their way across the lipid bilayer and sends

them back outside the cell, notes Geof-frey Chang of Scripps Research Institute.

He led the team of researchers that solved the

structure of mouse P-glycoprotein to 3.8-Å resolution (Science 2009, 323, 1718).

Yet the pump can also do good—for example, by sitting on the placental membrane, where it protects a growing fetus from toxic chemicals. In fact, the en-zyme’s dual role as both an essential shield and over-protective barricade is exemplified in the blood-brain barrier, where P-glycoprotein protects the brain from harmful chemicals in blood while also frustrating drug developers by kicking out possibly useful treatments for deadly brain diseases.

“This is very exciting work,” comments Stephan Wilkens, a biochemist at Upstate Medical University, in Syracuse, N.Y., who studies P-glycoprotein by electron microscopy. “Many laboratories and drug companies have been working for years on getting such a structure.”

Although the structure “is a great start” for drug de-velopers wishing to selectively block the pump, Wilk-ens adds, “the resolution of the side chains isn’t quite good enough to do structure-based drug design yet.”

Chang’s team found that the enzyme’s substrate-binding pocket is a large internal cavity, open to both the membrane and the inside of a cell, and that it is full of ar-omatic and hydrophobic amino acids. When they solved the structure in the presence of two stereoisomers of a greasy inhibitor, they found that the isomers bound in different parts of the binding cavity, showing just how promiscuous the protein transporter is.—SARAH EVERTS

K YOTO UNIVERSITY researchers have made an optically transparent paper from nanosized cellu-lose fibers. The renewable material’s transparency,

strength, and thermal stability give it potential advantages over glass or polymers for use in electronic devices.

Masaya Nogi, a postdoc in professor Hiroyuki Yano’s lab at the Research Institute for Sustainable Humano-sphere, presented the work before the Division of Cel-lulose & Renewable Materials on March 26 at the ACS national meeting in Salt Lake City.

Nogi and colleagues made nanofiber paper with cellulose, the material used to make traditional paper. But differences in fiber width and size of internal cavi-ties give the papers different physical properties, Nogi said. Nanofiber paper appears transparent because the fibers pack densely and create tiny spaces that avoid light scattering. Conventional paper is opaque be-cause the interstices between the fibers scatter light.

The new material bridges the gap in desirable prop-erties for electronic applications between traditional paper and glass or clear polymer films, says Margaret Frey, an associate professor of fiber science at Cornell University and session coorganizer.

Glass has thermal stability but lacks the flexibility desired in electronic displays, for example, whereas many flexible plastics are not thermally stable.

“Transparent substrates are needed for transparent electronics,” says Zhenan Bao, an associate professor of chemical engineering and an electronics expert at Stanford University. The nanofiber paper has thermal expandability comparable with that of glass, she says.

However, Frey adds, all cellulose would be flam-mable and hydrophilic without further treatment.

To make the densely packed nanofiber paper, Nogi and coworkers pressed a wood flour and water slurry into sheets that were dried and then polished with fine-grit sandpaper (Adv. Mater., DOI: 10.1002/adma.200803174). Hydrogen bonding of hydroxyl groups holds the cellulose fibers together.

Other researchers have created materials like trans-parent paper, but they were not as flexible or required complicated processing, says Derek G. Gray, a profes-sor in the chemistry department at McGill University, in Montreal. The new method “is a practical route to novel materials based on a key renewable resource,” he adds.—RACHEL PETKEWICH

Polished nanofiber paper folds like traditional paper.

NEWS OF THE WEEK

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CLEAR NANOFIBER PAPER

ACS MEETING NEWS: Cellulose-based material could be used for

flexible electronics

A CELL’S VACUUM CLEANER

CRYSTALLOGRAPHY: Researchers solve the structure of P-glycoprotein,

which kicks molecules out of cells

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The first crystal structure of a mammalian P-glycoprotein.