Shape changes in aroma-producing molecules determine the fragrances we detect (12/27/2008)
Shakespeare wrote "a rose by any other name
would smell as sweet." But would it if the molecules that generate its
fragrance were to change their shape?
That's what Dr. Kevin Ryan, Assistant Professor of Chemistry at The City
College of New York (CCNY) and collaborators in the laboratory of Dr. Stuart
Firestein, Professor of Biology at Columbia University, set out to
investigate. Their findings, reported today in the journal "Chemistry &
Biology," shed new insight into how our sense of smell works and have
potential 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 400
different varieties olfactory sensory neurons (OSN) housed in the nose's
internal membrane tissue, Professor Ryan explained. The unique reaction
pattern produced, known as the olfactory code, is sent as a signal to the
brain, which leads to perception of odors.
Professor Ryan and his team wanted to learn how these receptor cells respond
when odorants change their shape. They studied the odorant octanal, an
eight-carbon aldehyde that occurs in many flowers and citrus fruits. Octanal
is a structurally flexible molecule that can adapt to many different shapes
by rotating its chemical bonds.
The researchers designed and synthesized eight-carbon aldehydes that
resembled octanal, but had their carbon chains locked by adding one
additional bond. These molecules were tested on genetically engineered OSNs
known to respond to octanal. This work was done in Professor Firestein's
laboratory at Columbia.
The aldehyde molecules that could stretch to their greatest length triggered
strong activity in the OSNs. However, those molecules whose carbon chains
were constrained into a U shape blocked the receptor and left the cell
unable to sense octanal.
"Conformationally constrained odorants were more selective in the number of
OSNs they activated," Professor Ryan noted. "The results indicate that these
odorant molecules might be able to alter fragrance mixture odors in two
ways: by muting the activity of flexible odorants present in a mixture and
by activating a smaller subset of OSNs than chemically related flexible
odorants. This would produce a different olfactory code signature."
Olfactory receptors belong to the G-protein coupled receptor (GPCR) class of
proteins, a family of molecules found in cell membranes throughout the body.
Professor Ryan pointed out that half of all commercial pharmaceuticals work
by interaction with proteins within this family. Thus, the findings could
also have applications to GPCR drug design, as well.
Note: This story has been adapted from a news release issued by the City College of New York
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