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Clicking into place
CARLSBAD, Calif.—Click chemistry found its start in the laboratory of Nobel Laureate K. Barry Sharpless at The Scripps Research Institute in La Jolla, Calif. Now, it's playing a growing role in Invitrogen's efforts to build an-IP portfolio around click chemistry—a portfolio that got larger in December when the company announced it had secured an exclusive license from Harvard University for unique cell proliferation assays based on click chemistry.
Invitrogen already held a license for click chemistry from Scripps, and it also has secured commercial licenses from the University of California, Berkeley; the National Institutes of Health; and the California Institute of Technology to market kits for glycoprotein profiling based on Invitrogen's Click-iT labeling and detection technology, which uses a catalyst to "click" together chemical groups not normally found in biology. These kits enable researchers to label subsets of glycoproteins in live cells, extracts or purified samples—and are compatible with mass spectrometry.
The newer Click-iT EdU kit, based on technology invented by Drs. Adrian Salic and Tim Mitchison at the Harvard Medical School Department of Systems Biology uses EdU, a modified nucleic acid subunit that can be taken up by actively dividing cells and incorporating into newly synthesized DNA. A fluorescent small-molecule tag can then be snapped onto the EdU-labeled DNA to mark proliferating cells.
This click reaction is specific and efficient, Invitrogen reports, and molecules tagged by Click-iT molecules retain biological function and are easily detected at extremely low levels in complex samples. Click-iT chemistry is suitable for multiple applications, including flow cytometry, fluorescence microscopy and high-content screening.
Invitrogen is keen to gain more IP in the click chemistry space because it plans to develop additional Click-iT product line applications, including replacing radioactivity for detecting new protein synthesis, says Kathy Free, product manger for Invitrogen.
"This is an important area for Invitrogen, and we are definitely looking into several other areas to acquire additional click chemistry IP," Free says, noting that Click-iT technology is a good example of how Invitrogen is broadening its cellular biology product line and cementing its position as a leading provider of reagents for protein and cellular analysis. "We aren't willing to disclose just yet which specific areas we are heading into with click chemistry, but it's definitely part of our strategy moving forward."
"This technology fills a void left between radioactivity and fluorescence," Free adds. Filling that gap is important given the $325 million purchase of Molecular Probes Inc. in 2003, she says—along with its novel fluorescence-based technologies for labeling biological molecules in disease research and biopharmaceutical development.
"Traditional methods of specifically labeling cellular components require antibodies, which may be larger than the molecule a scientist is trying to visualize; this may compromise the function of that molecule," notes Augie Sick, vice president and general manager of Invitrogen's cellular analysis business unit. "On the other hand, direct fluorescent labeling will label your molecule of interest along with many others, making precise observations impossible. Click chemistry marries the specificity of antibodies with the flexibility of direct labeling, giving scientists new tools to probe into cellular function."
"Click chemistry will enable us, and our customers, to delve into discovery areas that used to be restricted to radioactive techniques," Free notes. "Researchers can now dig deeper into applications where there were no real solutions before, and they can have an option other than radioactive techniques now."