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Multicolor Live-Cell Chemical Imaging by Isotopically Edited Alkyne Vibrational Palette

Chen, Zhixing and Paley, Daniel W. and Wei, Lu and Weisman, Andrew L. and Friesner, Richard A. and Nuckolls, Colin and Min, Wei (2014) Multicolor Live-Cell Chemical Imaging by Isotopically Edited Alkyne Vibrational Palette. Journal of the American Chemical Society, 136 (22). pp. 8027-8033. ISSN 0002-7863. PMCID PMC4063185.

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Vibrational imaging such as Raman microscopy is a powerful technique for visualizing a variety of molecules in live cells and tissues with chemical contrast. Going beyond the conventional label-free modality, recent advance of coupling alkyne vibrational tags with stimulated Raman scattering microscopy paves the way for imaging a wide spectrum of alkyne-labeled small biomolecules with superb sensitivity, specificity, resolution, biocompatibility, and minimal perturbation. Unfortunately, the currently available alkyne tag only processes a single vibrational “color”, which prohibits multiplex chemical imaging of small molecules in a way that is being routinely practiced in fluorescence microscopy. Herein we develop a three-color vibrational palette of alkyne tags using a ^(13)C-based isotopic editing strategy. We first synthesized ^(13)C isotopologues of EdU, a DNA metabolic reporter, by using the newly developed alkyne cross-metathesis reaction. Consistent with theoretical predictions, the mono-^(13)C (^(13)C≡^(12)C) and bis-^(13)C (^(13)C≡^(13)C) labeled alkyne isotopologues display Raman peaks that are red-shifted and spectrally resolved from the originally unlabeled (^(12)C≡^(12)C) alkynyl probe. We further demonstrated three-color chemical imaging of nascent DNA, RNA, and newly uptaken fatty-acid in live mammalian cells with a simultaneous treatment of three different isotopically edited alkynyl metabolic reporters. The alkyne vibrational palette presented here thus opens up multicolor imaging of small biomolecules, enlightening a new dimension of chemical imaging.

Item Type:Article
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URLURL TypeDescription CentralArticle Information
Wei, Lu0000-0001-9170-2283
Min, Wei0000-0003-2570-3557
Additional Information:© 2014 American Chemical Society. ACS AuthorChoice - This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes. Received: March 17, 2014. Published: May 21, 2014. We thank F. Hu, Y. Shen, and M. Jimenez for helpful discussions. D.W.P. and C.N. acknowledge support from the Chemical Sciences, Geosciences and Biosciences Division, Office of Basic Energy Sciences, U.S. Department of Energy (DOE) under award number DE-FG02-01ER15264. W.M. acknowledges support from NIH Director’s New Innovator Award and Alfred P. Sloan Research Fellowship. The authors declare the following competing financial interest(s): Z.C., L.W., and W.M. are the inventors of a patent application filed by Columbia University. R.A.F. has an interest in Schrodinger, Inc. R.A.F. has a significant financial stake in Schrödinger, Inc., is a consultant to Schrödinger, Inc. and is on the Scientific Advisory Board of Schrödinger, Inc.
Funding AgencyGrant Number
Department of Energy (DOE)DE-FG02-01ER15264
Alfred P. Sloan FoundationUNSPECIFIED
Issue or Number:22
PubMed Central ID:PMC4063185
Record Number:CaltechAUTHORS:20181119-102039582
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Official Citation:Multicolor Live-Cell Chemical Imaging by Isotopically Edited Alkyne Vibrational Palette Zhixing Chen, Daniel W. Paley, Lu Wei, Andrew L. Weisman, Richard A. Friesner, Colin Nuckolls, and Wei Min Journal of the American Chemical Society 2014 136 (22), 8027-8033 DOI: 10.1021/ja502706q
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:91011
Deposited By: George Porter
Deposited On:19 Nov 2018 19:38
Last Modified:23 Oct 2019 20:52

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