Feb. 9, 1998 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 biological research.
"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 enzymatic action.
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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