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Scientists usually consider fluorescent labels on biomolecule delivery vehicles to be passengers along for the ride. But in some cases, those labels might actually be in the driver's seat. Caltech's Jacqueline K. Barton and Cindy A. Puckett have found that a ruthenium complex conjugated to the cell-penetrating peptide octaarginine displays different cellular uptake behavior when it is tagged with fluorescein (J. Am. Chem. Soc., DOI: 10.1021/ja9025165). The ruthenium complex is itself fluorescent, so the researchers can see the conjugate with or without the dye. Without fluorescein, the ruthenium-octaarginine conjugate remains outside the cell nucleus, although at high concentrations the octaarginine begins guiding the conjugate into the nucleus. With fluorescein, the conjugate is guided more quickly into the nucleus, even at low concentrations. A conjugate formed from fluorescein and the ruthenium complex, without octaarginine to guide it, doesn't travel into the nucleus. "It's a reminder that we really do have to worry about whether the tail is wagging the dog and how you are perturbing the system when you attach fluorescent probes," Barton says.
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