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

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.

• Authors: Joshua D Thomas, Thomas Hofer, Christoph Rader, Terrence R Burke Jr
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 18 Issue 21 Pg. 5785-8 (Nov 01 2008) ISSN: 1464-3405 [Electronic] England
• PMID: 18922692 (Publication Type: Journal Article, Research Support, N.I.H., Intramural)

Chemical References

• Antibodies
• Immunoconjugates
• Pharmaceutical Preparations

Topics

• Antibodies (chemistry)
• Enzyme-Linked Immunosorbent Assay
• Immunoconjugates (chemistry)
• Molecular Mimicry
• Molecular Structure
• Pharmaceutical Preparations (chemistry)