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Comparison of the C2A Domain of Synaptotagmin-I and Annexin-V As Probes for Detecting Cell Death
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    Comparison of the C2A Domain of Synaptotagmin-I and Annexin-V As Probes for Detecting Cell Death
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    Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, United Kingdom, and Cancer Research UK Cambridge Research Institute, Li-Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, United Kingdom
    * Corresponding author. Kevin M. Brindle, Department of Biochemistry, University of Cambridge, 80 Tennis Court Road, Cambridge CB2 1GA, UK., Tel: +44 (0)1223 333674, Fax: +44 (0)1223 766002, Email: [email protected]
    †Equal contributions.
    §Cancer Research UK Cambridge Research Institute.
    ‡University of Cambridge.
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    Bioconjugate Chemistry

    Cite this: Bioconjugate Chem. 2010, 21, 5, 884–891
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    https://doi.org/10.1021/bc9004415
    Published April 19, 2010
    Copyright © 2010 American Chemical Society

    Abstract

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    The induction of apoptosis is frequently accompanied by the exposure of phosphatidylserine (PS) on the cell surface, which has been detected using radionuclide and fluorescently labeled derivatives of the PS-binding protein, Annexin V. The fluorescently labeled protein has been used extensively in vitro as a diagnostic reagent for detecting cell death, and radionuclide-labeled derivatives have undergone clinical trials for detecting tumor cell death in vivo following treatment. We show here that the C2A domain of Synaptotagmin-I, which had been fluorescently labeled at a single cysteine residue introduced by site-directed mutagenesis, detected the same levels of cell death as a similarly labeled Annexin-V derivative, in drug-treated murine lymphoma and human breast cancer cell lines in vitro. However, the C2A derivative showed significantly less binding to viable cells and, as a consequence, up to 4-fold more specific binding to apoptotic and necrotic cells when compared with Annexin-V. C2A offers a potential route for the development of a new generation of more specific imaging probes for the detection of tumor cell death in the clinic.

    Copyright © 2010 American Chemical Society

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    Supporting Information

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    Expression and purification of C2A(S78C), the protein assay, electrospray ionization (ESI) mass spectrometry, and surface plasmon resonance (SPR) measurements are described in more detail. There is a table showing the dissociation constants derived from affinity and kinetic analysis of the SPR data, a figure showing the ESI−mass spectrum of the C2Am-AlxF647 conjugate, figures showing the SDS-PAGE gels of the C2Am-AlxF647 and AnxV-AlxF647 conjugates and a figure demonstrating the effect of probe concentration on the specificity of labeling with C2Am and AnxV. This material is available free of charge via the Internet at http://pubs.acs.org.

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    44. André A. Neves, Kevin M. Brindle. Imaging Cell Death. Journal of Nuclear Medicine 2014, 55 (1) , 1-4. https://doi.org/10.2967/jnumed.112.114264
    45. Alexander P. Demchenko. Beyond annexin V: fluorescence response of cellular membranes to apoptosis. Cytotechnology 2013, 65 (2) , 157-172. https://doi.org/10.1007/s10616-012-9481-y
    46. Francis G. Blankenberg, H. William Strauss. Recent Advances in the Molecular Imaging of Programmed Cell Death: Part I—Pathophysiology and Radiotracers. Journal of Nuclear Medicine 2012, 53 (11) , 1659-1662. https://doi.org/10.2967/jnumed.112.108944
    47. Dennis H. M. Kusters, Jan Tegtmeier, Leon J. Schurgers, Chris P. M. Reutelingsperger. Molecular Imaging to Identify the Vulnerable Plaque—From Basic Research to Clinical Practice. Molecular Imaging and Biology 2012, 14 (5) , 523-533. https://doi.org/10.1007/s11307-012-0586-7
    48. Falguni Basuli, Haitao Wu, Zhen-Dan Shi, Bao Teng, Changhui Li, Agnieszka Sulima, Aaron Bate, Philip Young, Mathew McMillan, Gary L. Griffiths. Synthesis of ApoSense compound [18F]2-(5-(dimethylamino)naphthalene-1-sulfonamido)-2-(fluoromethyl)butanoic acid ([18F]NST732) by nucleophilic ring opening of an aziridine precursor. Nuclear Medicine and Biology 2012, 39 (5) , 687-696. https://doi.org/10.1016/j.nucmedbio.2011.12.008
    49. Francis G. Blankenberg, Joseph F. Norfray. Multimodality Molecular Imaging of Apoptosis in Oncology. American Journal of Roentgenology 2011, 197 (2) , 308-317. https://doi.org/10.2214/AJR.11.6953
    50. Bryan A. Smith, Shuzhang Xiao, William Wolter, James Wheeler, Mark A. Suckow, Bradley D. Smith. In vivo targeting of cell death using a synthetic fluorescent molecular probe. Apoptosis 2011, 16 (7) , 722-731. https://doi.org/10.1007/s10495-011-0601-5
    51. Henning Stöckmann, André A. Neves, Shaun Stairs, Kevin M. Brindle, Finian J. Leeper. Exploring isonitrile-based click chemistry for ligation with biomolecules. Organic & Biomolecular Chemistry 2011, 9 (21) , 7303. https://doi.org/10.1039/c1ob06424j
    52. Gang Niu, Xiaoyuan Chen. Apoptosis Imaging: Beyond Annexin V. Journal of Nuclear Medicine 2010, 51 (11) , 1659-1662. https://doi.org/10.2967/jnumed.110.078584
    53. Quang-Dé Nguyen, Eric O. Aboagye. Imaging the life and death of tumors in living subjects: Preclinical PET imaging of proliferation and apoptosis. Integrative Biology 2010, 2 (10) , 483. https://doi.org/10.1039/c0ib00066c

    Bioconjugate Chemistry

    Cite this: Bioconjugate Chem. 2010, 21, 5, 884–891
    Click to copy citationCitation copied!
    https://doi.org/10.1021/bc9004415
    Published April 19, 2010
    Copyright © 2010 American Chemical Society

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