Taking inspiration from nature, University of Wisconsin-Madison chemists have found a powerful way to wrangle long, snaking molecules to form large rings—rings that shape the spine of many pharmaceuticals; however, are troublesome to supply within the lab on December 19
The work could represent preliminary progress toward deciphering how enzymes, honed by evolution, so efficiently produce pure compounds. More instantly, the brand new technique may help researchers synthesize medication which has extensive ring backbones, including those for hepatitis. The study is printed in the journal Science on December 19.
Nature prefers the disorder of a flexible, long molecule to the order of an inflexible ring, which makes it difficult for chemists to manipulate large rings to shape in the lab. “If the linear molecules get long sufficient, it’s as if the ends don’t know anymore that they are connected, and they’re likely to bond with other molecules as they’re to come together,” says UW-Madison Chemistry professor Sam Gellman, the author of the report.
Yet biological enzymes can bring these ends collectively and form rings of all sizes. They accomplish this feat due to their complex, 3D shapes that act as a lock—the linear molecule fits into place like a key for an organized reaction to happen.
To research how enzymes work as well as mimic their abilities, Gellman’s group turned to a lot smaller, 3D protein-like molecules called foldamers that their lab has helped create.
Because the foldamer has a 3D form that can grab on to the ends of the flexible precursor molecule, it tremendously increases the odds that the ends find each other.