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Stable and Potent Selenomab-Drug Conjugates

  1. Author:
    Li, Xiuling
    Nelson, Christopher
    Nair, Rajesh R
    Hazlehurst, Lori
    Moroni, Tina
    Martinez-Acedo, Pablo
    Nanna, Alex R
    Hymel, David
    Burke, Terrence
    Rader, Christoph

  2. Author Address

    Department of Cancer Biology, The Scripps Research Institute, Jupiter, FL 33458, USA., Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA., Molecular Oncology Program, H. Lee Moffitt Cancer Center, Tampa, FL 33612, USA., Proteomics and Mass Spectrometry Core, The Scripps Research Institute, Jupiter, FL 33458, USA., Department of Cancer Biology, The Scripps Research Institute, Jupiter, FL 33458, USA; Department of Molecular Therapeutics, The Scripps Research Institute, Jupiter, FL 33458, USA. Electronic address: crader@scripps.edu.,
    1. Year: 2017
    2. Date: Apr 20
    3. Epub Date: 2017 Mar 09
  2. Journal: Cell Chemical Biology
    1. 24
    2. 4
    3. Pages: 433-442
  4. Type of Article: Article
  1. Abstract:

    Selenomabs are engineered monoclonal antibodies with one or more translationally incorporated selenocysteine residues. The unique reactivity of the selenol group of selenocysteine permits site-specific conjugation of drugs. Compared with other natural and unnatural amino acid and carbohydrate residues that have been used for the generation of site-specific antibody-drug conjugates, selenocysteine is particularly reactive, permitting fast, single-step, and efficient reactions under near physiological conditions. Using a tailored conjugation chemistry, we generated highly stable selenomab-drug conjugates and demonstrated their potency and selectivity in vitro and in vivo. These site-specific antibody-drug conjugates built on a selenocysteine interface revealed broad therapeutic utility in liquid and solid malignancy models. Copyright © 2017 Elsevier Ltd. All rights reserved.

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External Sources

  1. View Full Text
  2. DOI: 10.1016/j.chembiol.2017.02.012
  3. PMID: 28330604
  4. View record in Web of Science®
  5. WOS: 000400007300004

Library Notes

  1. Fiscal Year: FY2016-2017
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