The demolition drug: trashing faulty proteins

时间:2019-03-02 06:17:04166网络整理admin

By Robin Orwant IT WAS a meeting that might transform medicine. In 1998, biochemists Craig Crews and Raymond Deshaies starting chatting at a conference at the Semiahmoo Resort on the picturesque coast of Washington state. “After a few beers, we started doing some wishful thinking,” says Crews. “And we came up with something new.” Their idea was to create a new kind of drug – one that could target and destroy proteins by hijacking cells’ own machinery. “After a few beers we came up with something new. If it works, it will be revolutionary” Deshaies started writing a research proposal almost as soon as he got back to his lab at the California Institute of Technology in Pasadena. Now, more than seven years on, he and Crews – of Yale University – are getting tantalisingly close to achieving their goal. “If this works,” says Deshaies, “it will be completely revolutionary.” Almost all drugs work by interfering with proteins. Some bind to and block the active site on an enzyme, others prevent signalling molecules from binding to a receptor. They all consist of small molecules that can easily get into the bloodstream and then into cells. But the active site of a protein is a tiny target, so finding small molecules that bind to it and it alone is not easy. And cancers, viruses and bacteria often mutate and become resistant to drugs. Worse still, a huge number of proteins do not work in a way that is easy to inhibit – many interact via domains far larger than an active site,