Contact: Bob Nelson For immediate release
Columbia Chemist Develops Fluorescing Sensors;
Applications Seen in Medical Diagnostics, Research
A Columbia University chemist has built molecular sensors that glow
bright green when they bind to the substance they are designed to detect.
Two such new sensors have been developed by Clark Still, professor of
chemistry, and his research team and are described in the Feb. 6 issue of the
journal Science. The sensors, when developed into a family of laboratory tools,
could have applications in medical diagnostics, environmental sensing and
"What we've worked with so far are peptides, but if we can bind peptides, we
should be able to bind proteins," Professor Still said, since peptides are the
components of proteins. "But the particular sensors we've made can detect things
other than proteins and peptides. The applications are potentially very exciting."
The highly accurate, molecular-level sensors could be used to detect the
presence of certain proteins in blood plasma or other biological fluids. They could
also be used to construct a chemical nose, an environmental detector that would
report the presence of certain substances in the air with extremely high accuracy.
Additionally, the sensor molecules could be placed inside cells to detect the
presence of neurotransmitters, hormones or other small biological molecules,
giving medical researchers new insights into cell functioning.
The sensors constructed so far precisely detect tripeptides, chains of three
amino acids. There are only 20 amino acids, though each exists in right- and left-
hand forms. Chains of amino acids make up peptides, and blocks of peptides link
together to form proteins, some of the most common substances in the human
body, forming every internal structure and promoting metabolism through
The particular sensors Professor Still developed are chemicals with peptide
binding sites that are equipped with a fluorescing molecular fragment on one side
and a quenching fragment that controls the fluorescence on the other. When a
chemical substance binds to the site, the fluorescing fragment is separated from
the quenching fragment and fluorescence is enhanced, resulting in a three- to
five-times increase in light emission.
Professor Still and his team - former postdoctoral fellows Chao-Tsen Chen
and Holger Wagner - developed small-molecule peptide-binding receptors in the
laboratory, and then added the fluorescing and quenching fragments on either
side of the receptors' concave binding sites. The first sensor detects only two
specific amino acid sequences from a library of 3,375 tripeptides: proline-valine-
glycine and lysine-valine-proline. The second chemical sensor was less
discriminating, binding to eight of the tripeptides in the library.
The sensors are extraordinarily sensitive, detecting the presence of
recognized peptides at micromolar concentrations, or one one-thousandth of the
tripeptide's molecular weight in grams dissolved in one liter of solution.
Finally, the Columbia team created a solid-state version of the chemical
sensors, placing derivatives of the sensors on polystyrene beads and fixing them to
solid supports at the bottom of a Petri dish. Examined with a fluorescence
microscope, the beads glowed bright green when exposed to the tripeptide
sequences in question.
The work is supported by the Office of Naval Research.
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