RAPID TAGGING OF BIOMOLECULES - C&EN Global Enterprise

Oct 6, 2008 - Together with Melissa L. Blackman and Maksim Royzen, Fox has developed a new labeling reaction based on the cycloaddition of ...
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LAW PROTECTS RESEARCHERS SECURITY: California bill makes it

illegal to publish academics’ information for criminal intent

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An FBI agent removes crimescene tape after a firebomb attack on a UCSC researcher.

HE AUGUST BOMB ATTACKS on the homes of two University of California, Santa Cruz, researchers has spurred the swift passage of a new California law making it illegal to publish the names and addresses of academic researchers and their families with the intent to commit a violent crime. The Researcher Protection Act, which was written by Assembly member Gene Mullin (D-South San Francisco), also forbids people from entering academic researchers’ homes “with the intent to disrupt, preventing the exercise of, or interfering with the researcher’s academic freedom.” The bill, known as A.B. 2296, was introduced in February and had been wending its way through the legislative process. It then got a boost in August when

RAPID TAGGING OF BIOMOLECULES

Protein

CHEMICAL BIOLOGY: Cycloaddition never before used biologically could help assemble sophisticated probes

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Y ADAPTING a cycloaddition reaction that has never been used in biological systems, chemists have developed an exceptionally fast method for labeling biomolecules such as proteins. The advance could aid the study of dynamic processes in living systems. Biomolecules inside cells usually exist at low concentrations. To get a glimpse of cellular goings-on, researchers label biomolecules with fluorescent or other tags. The tagging must be fast to be useful in living systems, says Joseph M. Fox, a chemist at the University of Delaware. Together with Melissa The cycloaddition of L. Blackman and Maksim a trans-cyclooctene Royzen, Fox has developed to a tetrazine gives a new labeling reaction off nitrogen gas and rapidly labels a protein based on the cycloaddition of biomolecules derivatized in a dilute solution. WWW.C E N- ONLI NE .ORG

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bombs destroyed the car of one UCSC biomedical researcher and the front of the off-campus house of UCSC assistant professor David Feldheim, who is in the department of molecular, cell, and developmental biology. Both researchers were believed to be targeted by animal-rights extremists (C&EN, Aug. 11, page 11). Gov. Arnold Schwarzenegger signed the bill into law on Sept. 29. Mullin says he’s “very pleased” the governor signed the bill. In addition to the recent attacks at UCSC, there have been other high-profile attacks and threats in recent years aimed at academics at other UC campuses. The new law is designed to have more teeth than the Federal Animal Enterprise Terrorism Act, which was passed in November 2006. Under the new law, actions such as the distribution of leaflets found in a Santa Cruz coffee shop shortly before the bombings, naming and threatening 13 UCSC researchers, including chemistry professor Pradip K. Mascharak, would now be criminalized in California. “This law will provide law enforcement with some of the tools necessary to help protect academic researchers so they can continue to perform groundbreaking research without the threat of violence,” UC President Mark G. Yudof said in a statement. UCSC chemistry department Chair Ólöf Einarsdóttir applauded the signing of the new law. “I am a mother as a well as a professor,” she says. “I think it’s important for young people who want to enter into science to know they will be protected.”—ELIZABETH WILSON

with trans-cyclooctene to a nitrogen-rich heterocycle called a tetrazine. The reaction needs no catalyst and is hundreds of times faster than click reactions, an established tagging method. What’s more, the tetrazine and cyclooctene don’t undergo side reactions with other molecules in biological systems. Fox’s method stands out for its selectivity and speed, says chemical biologist Carolyn R. Bertozzi of the University of California, Berkeley. The reaction’s kinetics are unprecedented, perhaps the fastest reported for such labeling reactions to date, she says. Although fast cycloadditions between tetrazines and cyclooctenes are known, the tetrazines used in those methods react with water and are therefore unsuitable for labeling in cells. Fox’s team tuned the tetrazine’s reactivity by adding pyridine moieties and showed that the revamped tetrazine reacts quickly and selectively with transcyclooctene in cell lysates. Moreover, the team labeled biologically relevant concentrations of a cyclooctenetagged protein with low concentrations of their tetrazine within minutes, a result suggesting the reaction could be applicable in cellular environments. Fox’s work “is an elegant demonstration of how classic chemistry from the physical organic literature can be artfully retrofitted for modern applications,” Bertozzi says.—CARMEN DRAHL

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