NEW YORK, December 22, 2008 - Shakespeare wrote "a rose by any other namewould smell as sweet." But would it if the molecules that generate itsfragrance were to change their shape?
That's what Dr. Kevin Ryan, Assistant Professor of Chemistry at The CityCollege of New York (CCNY) and collaborators in the laboratory of Dr. StuartFirestein, Professor of Biology at Columbia University, set out toinvestigate. Their findings, reported today in the journal "Chemistry &Biology," shed new insight into how our sense of smell works and havepotential applications in the design of flavors and fragrances.
When odor-producing molecules, known as odorants, pass through the nose,they trigger intracellular changes in a subset of the approximately 400different varieties olfactory sensory neurons (OSN) housed in the nose'sinternal membrane tissue, Professor Ryan explained. The unique reactionpattern produced, known as the olfactory code, is sent as a signal to thebrain, which leads to perception of odors.
Professor Ryan and his team wanted to learn how these receptor cells respondwhen odorants change their shape. They studied the odorant octanal, aneight-carbon aldehyde that occurs in many flowers and citrus fruits. Octanalis a structurally flexible molecule that can adapt to many different shapesby rotating its chemical bonds.
The researchers designed and synthesized eight-carbon aldehydes thatresembled octanal, but had their carbon chains locked by adding oneadditional bond. These molecules were tested on genetically engineered OSNsknown to respond to octanal. This work was done in Professor Firestein'slaboratory at Columbia.
The aldehyde molecules that could stretch to their greatest length triggeredstrong activity in the OSNs. However, those molecules whose carbon chainswere constrained into a U shape blocked the receptor and left the cellunable to sense octanal.
"Conformationally constrained odorants were more selective in the number ofOSNs they activated," Professor Ryan noted. "The results indicate that theseodorant molecules might be able to alter fragrance mixture odors in twoways: by muting the activity of flexible odorants present in a mixture andby activating a smaller subset of OSNs than chemically related flexibleodorants. This would produce a different olfactory code signature."
Olfactory receptors belong to the G-protein coupled receptor (GPCR) class ofproteins, a family of molecules found in cell membranes throughout the body.Professor Ryan pointed out that half of all commercial pharmaceuticals workby interaction with proteins within this family. Thus, the findings couldalso have applications to GPCR drug design, as well.
Source: City College of New York