A novel bifunctional maleimido CHX-A'' chelator for conjugation to thiol-containing biomolecules

Bioorg Med Chem Lett. 2008 Apr 15;18(8):2679-83. doi: 10.1016/j.bmcl.2008.03.022. Epub 2008 Mar 10.

Abstract

A novel bifunctional maleimido CHX-A'' DTPA chelator 5 was developed and conjugated to the monoclonal antibody trastuzumab (Herceptin) and subsequently radiolabeled with (111)In. The resulting (111)In labeled immunoconjugate 2 was demonstrated to bind to SKOV-3 ovarian cancer cells comparably to an isothiocyanato CHX-A'' DTPA modified native trastuzumab, 1. Through efficient thiol-maleimide chemistry, antibodies, peptides or other targeting vectors can now be modified with an established radioactive metal chelating agent CHX-A'' DTPA for imaging and/or therapies of cancer.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Antibodies, Monoclonal / chemistry
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal, Humanized
  • Cell Line, Tumor
  • Chelating Agents / chemical synthesis
  • Chelating Agents / chemistry*
  • Chromatography, High Pressure Liquid
  • Humans
  • Isothiocyanates / chemical synthesis
  • Isothiocyanates / chemistry*
  • Maleimides / chemistry*
  • Molecular Structure
  • Pentetic Acid / analogs & derivatives*
  • Pentetic Acid / chemical synthesis
  • Pentetic Acid / chemistry
  • Sulfhydryl Compounds / chemistry*
  • Sulfhydryl Compounds / metabolism*
  • Trastuzumab

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Chelating Agents
  • Isothiocyanates
  • Maleimides
  • Sulfhydryl Compounds
  • N-(2-amino-3-(4-isothiocyanatophenyl)propyl)cyclohexane-1,2-diamine-N,N',N',N'',N''-pentaacetic acid
  • maleimide
  • Pentetic Acid
  • Trastuzumab