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Alkyne-Tagged Raman Probes for Local Environmental Sensing by Hydrogen–Deuterium Exchange

Bi, Xiaotian and Miao, Kun and Wei, Lu (2022) Alkyne-Tagged Raman Probes for Local Environmental Sensing by Hydrogen–Deuterium Exchange. Journal of the American Chemical Society, 144 (19). pp. 8504-8514. ISSN 0002-7863. doi:10.1021/jacs.2c01991.

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Alkyne-tagged Raman probes have shown high promise for noninvasive and sensitive visualization of small biomolecules to understand their functional roles in live cells. However, the potential for alkynes to sense cellular environments that goes beyond imaging remains to be further explored. Here, we report a general strategy for Raman imaging-based local environment sensing by hydrogen–deuterium exchange (HDX) of terminal alkynes (termed alkyne-HDX). We first demonstrate, in multiple Raman probes, that deuterations of the alkynyl hydrogens lead to remarkable shifts of alkyne Raman peaks for about 130 cm–1, providing resolvable signals suited for imaging-based analysis with high specificity. Both our analytical derivation and experimental characterizations subsequently establish that HDX kinetics are linearly proportional to both alkyne pKas and environmental pDs. After validating the quantitative nature of this strategy, we apply alkyne-HDX to sensing local chemical and cellular environments. We establish that alkyne-HDX exhibits high sensitivity to various DNA structures and demonstrates the capacity to detect DNA structural changes in situ from UV-induced damage. We further show that this strategy is also applicable to resolve subtle pD variations in live cells. Altogether, our work lays the foundation for utilizing alkyne-HDX strategy to quantitatively sense the local environments for a broad spectrum of applications in complex biological systems.

Item Type:Article
Related URLs:
URLURL TypeDescription
Bi, Xiaotian0000-0003-4449-7488
Miao, Kun0000-0001-6567-3650
Wei, Lu0000-0001-9170-2283
Additional Information:© 2022 American Chemical Society. Received 21 July 2021. Published online 4 May 2022. Published in issue 18 May 2022. We acknowledge the Caltech Biological Imaging Facility for providing the instrument. We thank Prof. Jacqueline Barton, Prof. Jesse Beauchamp, Amy-Doan P. Vo, Jiajun Du, Jolena Zhou, and Heyun Li for fruitful discussions. L.W. is a Heritage Principal Investigator supported by the Heritage Medical Research Institute. L.W. also acknowledges the support of the start-up funds from the California Institute of Technology and the Shurl and Kay Curci Foundation grant. The authors declare no competing financial interest.
Group:Heritage Medical Research Institute
Funding AgencyGrant Number
Heritage Medical Research InstituteUNSPECIFIED
Shurl and Kay Curci FoundationUNSPECIFIED
Subject Keywords:Genetics, Hydrocarbons, Kinetics, Oligomers, Probes
Issue or Number:19
Record Number:CaltechAUTHORS:20220520-649607000
Persistent URL:
Official Citation:Alkyne-Tagged Raman Probes for Local Environmental Sensing by Hydrogen–Deuterium Exchange Xiaotian Bi, Kun Miao, and Lu Wei Journal of the American Chemical Society 2022 144 (19), 8504-8514 DOI: 10.1021/jacs.2c01991
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:114830
Deposited By: George Porter
Deposited On:20 May 2022 21:15
Last Modified:20 May 2022 21:15

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