NEWS OF THE WEEK BIOCHEMISTRY
CAN-DO CATALYSTS All-in-vitro method selects catalytic antibodies with enzymelike efficiency
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TEAM OF EUROPEAN sci
entists has come up with what they think is an im proved way to obtain highly effi cient antibody catalysts. Using their all-in-vitro method, gradu ate student Sandro Cesaro-Tadic and biochemistry professor An dreas Pluckthun of the Universi ty of Zurich; chemistry professor G. Michael Blackburn of the Uni versity of Sheffield, in England; and their coworkers have isolat ed a catalytic antibody capable of hydrolyzing phosphate monoesters [Nat. BiotechnoL, published online May 18, http://dx.doi.org/ 10.1038/nbt828}. Their approach combines and improves upon several techniques that have already been reported: a fully synthetic antibody library withgreater diversity than libraries obtained from mammalian im mune systems, directed evolution to make further improvements to the best candidates from a library and a selection method based di rectly on enzymatic turnover. "Instead of extrapolating from established techniques what might one day be possible, we have actu ally done it," they tell C&EN. The researchers begin with a library of 2 Χ 109 synthetic anti bodies, each displayed on the sur
ALTERNATIVE
face ofa virus called a phage. They expose these phage-tethered an tibodies to immobilized 2-difluo-
Catalytic antibody
"Catalytic antibody-virus
Nu = nucleophile
T R A P P E D Virus-tethered antibodies that can cleave the phosphate ester bond of an immobilized phosphate create a highly reactive product that bonds to the very antibody that produced it. Those antibodies can then be subjected to further rounds of selection.
romethylphenyl phosphate. Those antibodies that can cleave the an chored substrate's phosphate es ter bond produce a highly reactive intermediate that quickly traps the catalyst. Antibodies that succeed remain stuck to the surface, while those that fail are washed away The catalytically most active an-
FUELS
UPS To Give Fuel Cells A Try
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fuel-cell-powered delivery truck is scheduled to be on the road by the end of the year in Ann Arbor, Mich., through a collaboration of DaimlerChrysler, UPS, Air Products, and EPA. The demonstration project, announced in Michigan last week, will begin with an automobile-size express delivery vehicle and grow to include at least one Dodge Sprint van in 2004. The idea, the promoters say, is to provide a real-world test to assess fuel-cell vehicles. Compressed hydrogen for the truck will be supplied at a sta
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tibody undergoes further rounds ofrandom mutagenesis and selec tion to improve its activity The result is a phosphataselike catalytic antibody with 1,000-fold higher catalytic effi ciency than other catalytic anti bodies for this inherently diffi cult reaction. Still, its catalytic efficiency remains only one-tenthousandth that of alkaline phos-
phatase, the enzyme nature uses. The team hopes to further im prove its antibody's catalytic prowess by improving the anti body's affinity for substrate. In addition, Blackburn says the strategy can be easily adapted for other reactions and applied to even larger libraries.-AM AN DA YARN ELL
tion to be built by Air Products at EPA's Ann Arbor vehicle-test ing facility. It will be similar to the world's first hydrogen station that Air Products opened last year in Las Vegas (C&EN, Dec. 2, 2002, page 24). Several environmental groups picketed an EPA-organized press event in Michigan to announce the deal, however. They criticized the Bush Administration for backing fuel-cell pro grams that are years from a payoff while showing little interest in fuel efficiency standards or other immediate technologies. It was a big week for delivery truck demonstration projects. Another one was announced by Environmental Defense, involving 20 hybrid electric-diesel delivery vans to be used by FedEx Corp. with power systems built by Eaton Corp.—JEFF JOHNSON
C & E N / MAY 26, 2003
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