For drug makers, new 3-D control opens wealth of options

A team of scientists anchored at Yale University has demonstrated a new, highly versatile approach for quickly assembling drug-like compounds, establishing a broad new route to drug discovery and medical treatment. They report their results in the journal Science on Feb 8.

Drug molecules interact with their targets, such as proteins or enzymes, by attaching to them in a way that neutralizes the target's undesirable effects in the body. This is sometimes called the "lock-and-key" method. The new approach offers scientists far greater control over the three-dimensional structure of a key class of , making it easier to fashion that fit their targets in the right way.

"Now we've got a lot more control over the shape and orientation of this class of , and this essentially gives us greater flexibility in creating effective drugs," said Jonathan Ellman, the Yale chemist who led the experiment.

The research reported in Science revolves around piperidines, a class of widely used in pharmaceuticals, including the familiar drugs quinine, morphine, oxycodone, Plavix, Cialis, and Aricept. Piperidines are core structures, or scaffolds, upon which —parts of the drug molecule—can be displayed for binding to a drug's targets. The scientists have shown a way to generate different piperidine derivatives by varying acid strength.

"Our research allows us to make new piperidines easily," Ellman said. "The approach has biomedical relevance because the scaffold upon which the fragments are displayed is present in many of the most important drugs."

The research is being published without patent constraints and could be used by drug developers immediately, said Ellman, who is the Eugene Higgins Professor of Chemistry and professor of pharmacology. "I believe that this is the most effective approach for rapidly translating this work into new drugs," he said.

More information: "Proton Donor Acidity Controls Selectivity in Nonaromatic Nitrogen Heterocycle Synthesis," Science, 2013.

Related Stories

Cancer's next magic bullet may be magic shotgun

Jun 15, 2012

A new approach to drug design, pioneered by a group of researchers at the University of California, San Francisco (UCSF) and Mt. Sinai, New York, promises to help identify future drugs to fight cancer and other diseases that ...

New computational technique can predict drug side effects

Dec 11, 2007

Early identification of adverse effects of drugs before they are tested in humans is crucial in developing new therapeutics, as unexpected effects account for a third of all drug failures during the development process.

Hitting moving RNA drug targets

Jun 26, 2011

By accounting for the floppy, fickle nature of RNA, researchers at the University of Michigan and the University of California, Irvine have developed a new way to search for drugs that target this important molecule. Their ...

Recommended for you

Most US babies get their vaccines, CDC says

Aug 28, 2014

(HealthDay)—The vast majority of American babies are getting the vaccines they need to protect them from serious illnesses, federal health officials said Thursday.

Expression of privilege in vaccine refusal

Aug 27, 2014

Not all students returning to school this month will be up to date on their vaccinations. A new study conducted by Jennifer Reich, a researcher at the University of Colorado Denver, shows that the reasons why children may ...

User comments