David Nagib |
But creating those rings and forming them in a way that is tailored to each individual disease has always been a cumbersome and expensive process in medicinal chemistry.
New research, published today in the journal Chem, proposes a way to simplify that transformation. The discovery will likely make it easier to produce new drug candidates, the researchers say.
David Nagib, senior author of the study and associate professor of chemistry at The Ohio State University, likened the chain of molecules to a belt with no holes: With no way to fasten the circle and no measurements for where holes might go, the belt can’t be assembled in a way that keeps it closed.
“The problem we were trying to solve is how do you punch the hole so that it fits you perfectly, and get it right on the first try without measuring,” Nagib said. “The trick here was we had to put the holes in just the right place, but we had to figure out precisely where the holes should go, without any markings to tell us where that might be.”
The “belt” in this case is a string of carbon-hydrogen bonds, the most ubiquitous bonds in all of nature and medicines. Most drugs contain rings of carbon-hydrogen bonds, linked together by a “bridging” nitrogen atom, within complex structures that interact precisely with cellular components in the body – like a key fitting into a lock. The most common ring found in all medications are six-sided ones, called a piperidine.
But piperidines have long been difficult and expensive to produce, primarily because chemists could not quickly or cheaply replace a carbon-hydrogen bond with other chemical bonds.