The New Process Offers Tremendous Promise for Developing Novel Drug Molecules
NEW YORK /PRNewswire/ -- New drug discovery has been limited by researchers' inability to control a molecules' 3D structure. But a team of scientists from The Graduate Center of The City University of New York (GC/CUNY) has made a breakthrough in chemical synthesis that now makes it possible to quickly and reliably modify a molecule's 3D structure, according to a paper in Friday's issue of Science.
The work builds on the Nobel Prize-winning discovery by chemist Akira Suzuki, who pioneered development of cross-coupling reactions, which use palladium catalysts to bond carbon atoms. Suzuki's original discovery has enabled the rapid construction of novel molecules for drug research, but is largely limited to construction of flat (or 2D) molecules. That limitation has prevented scientists from easily manipulating a molecule's 3D structure for drug development.
"Two molecules that have the same structure and composition but are mirror images of each other can produce very different biological responses. Therefore, controlling the orientation of atoms in a molecule's 3D structure is critical in drug discovery," said research project director and corresponding author Mark Biscoe, an associate professor of chemistry with GC/CUNY and City College of New York. "The thalidomide tragedy in the 1950s and '60s arose because of the different biological effects of thalidomide's two mirror images. Today, cross-coupling reactions are employed extensively in drug discovery, but they haven't enabled control of 3D molecular structures. Our new process achieves this control, permitting selective formation of both mirror images of a molecule."
GC/CUNY researchers collaborated with University of Utah researchers to develop statistical models that predict chemical process reaction outcomes. They applied these models to develop conditions that enable control of 3D molecular structures. Key to their process was understanding the effects of different phosphine additives on how palladium promotes cross-coupling reactions. This allowed them to develop methods for selectively retaining a molecule's 3D geometry during a cross-coupling reaction, or to invert it to produce its mirror image, thereby controlling the molecule's final geometry.
This new method addresses significant challenges to drug discovery by allowing scientists to employ cross-coupling reactions to generate new compounds while controlling their 3D architecture. This will greatly facilitate discovery and development of new medicines.
Media Contacts: Shawn Rhea, srhea@gc.cuny.edu
SOURCE The Graduate Center of The City University of New York
