Beating Cancer to the Punch

Ahmed Awad, Ph.D.

Photo Compliments of the 

CI Chemistry Department

Ever wonder what would have happened if Marty McFly didn’t reunite his parents in Back to the Future? He wouldn’t exist of course! Dr. Ahmed Awad and 8 students at CI are on the hunt for ways to best cancer before it exists by developing drugs that specialize in inhibiting gene expression without the use of a DeLorean.

Some drugs target the protein after it has already formed; however, Awad and his team have a very different approach. “Our target is the messenger RNA,” Awad explained. The drugs consist of small segments of nucleic acids called oligonucleotides, which target the messenger RNA in carcinomic cells. The oligonucleotides react with the RNA by Watson-Crick base pairing via two mechanisms. The first mechanism blocks the translation into the protein. The second mechanism activates an enzyme called RNase H, which degrades the RNA/DNA complex.

“Chemical modifications are important to stabilize these drugs,” Awad noted. Reagents must be stabilized against nucleases, enzymes that cause nucleic acids to degrade. Nucleases are capable of degrading injected oligonucleotides within 5 minutes of injection, before the drug can reach its destination.

With any luck the next generation of these gene-inhibiting drugs will succeed in telling cancer to make like a tree, and get outta here.

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Achievement Unlocked

Solved structure for the M-PMV retroviral protease
University of Washington

From battling asteroids to battling AIDS, video games have come a long way. Using an internet based cooperative game called Fold It, online gamers have managed to solve the structure of an enzyme that has baffled scientists for more than ten years.

Like HIV, Mason-Pfizer monkey virus (M-PMV) causes AIDS in monkeys and apes. A M-PMV retroviral protease, a protein-cutting enzyme, is a key element for the spread of the virus in rhesus monkeys. After numerous attempts with molecular replacement techniques and years of frustration, scientists asked for the help from the Fold It gaming community.

Fold it is designed to utilize the special reasoning skills of warm blooded human beings to find the lowest energy state for a given molecule. It works by assigning points to players as they discover lower energy states for structures within a specified framework that reflects the laws of nature and chemistry. In this case a team of Fold It players solved the structure in less than 10 days time. According to a paper titled Crystal Structure of a Monomeric Retroviral Protease Solved by Protein Folding Game Players that was published in the September 18th, 2011 edition of Nature Structural & Molecular Biology, the structure discovered was “of sufficient quality for successful molecular replacement and subsequent structure determination.”

As a former Tetris addict, I am excited at the prospect that the worlds of video games and science are becoming complimentary. As long as there are tasks and puzzles that human brains can tackle and computer processors cannot there will be a place for citizen science. Who knew that solving proteins could be as fun as saving Princess Peach?

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