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Application of a trifunctional reactive linker for the construction of antibody-drug hybrid conjugates

Academic Article
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Overview

authors

  • Thomas, J. D.
  • Hofer, T.
  • Rader, Christoph
  • Burke, T. R.

publication date

  • November 2008

journal

  • Bioorganic & Medicinal Chemistry Letters  Journal

abstract

  • A flexible, trifunctional poly(ethylene glycol)-succinamide-Lysine-Lysine-maleimide (PEG-SU-Lys-Lys-mal) linker was employed to simultaneously allow biotin tagging and cell-surface targeting through an integrin alpha(4)beta(1)-binding peptidomimetic that was regiospecifically conjugated to an IgG1-derived Fc fragment with an engineered C-terminal selenocysteine residue. The resulting antibody derivative mediates Fc receptor binding by virtue of the Fc protein and selectively targets cancer cells expressing human integrin alpha(4)beta(1). The PEG-SU-Lys-Lys-mal linker may have general utility as an organic tether for the construction of antibody-drug conjugates.

subject areas

  • Antibodies
  • Enzyme-Linked Immunosorbent Assay
  • Immunoconjugates
  • Molecular Mimicry
  • Molecular Structure
  • Pharmaceutical Preparations
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Research

keywords

  • Fc
  • IgG1
  • Immunoconjugate
  • Integrin
  • LLP2A
  • Peptidomimetic
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Identity

PubMed Central ID

  • PMC3461582

International Standard Serial Number (ISSN)

  • 0960-894X

Digital Object Identifier (DOI)

  • 10.1016/j.bmcl.2008.09.078

PubMed ID

  • 18922692
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Additional Document Info

start page

  • 5785

end page

  • 5788

volume

  • 18

issue

  • 21

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