Simplified method for conjugating macrocyclic bifunctional chelating agents to antibodies via 2-iminothiolane

Bioconjug Chem. May-Jun 1990;1(3):222-6. doi: 10.1021/bc00003a007.


A one-step method for conjugating macrocyclic chelators to antibodies using the protein modification reagent 2-iminothiolane controls aggregation, maintains immunoreactivity, and produces consistent chelate/antibody ratios. Conjugation conditions have been investigated with the macrocyclic chelates 6-[p-(bromoacetamido)benzyl]-1,4,8,11-tetraazacyclotetradecane-N,N ',N",N"'-tetraacetic acid and 2-[p-(bromoacetamido)benzyl]-1,4,7,10-tetraazacyclododecane-N,N',N ",N"'-tetraacetic acid, with three different monoclonal antibodies. The bifunctional chelating agents are prepared by bromoacetylation of their amine precursors using a two-phase H2O/CHCl3 system, which improves product purity.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antibodies, Monoclonal / chemistry*
  • Antibody Affinity
  • Chelating Agents / chemistry*
  • Chromatography, High Pressure Liquid
  • Cobalt Radioisotopes
  • Cross-Linking Reagents*
  • Heterocyclic Compounds / chemistry*
  • Imidoesters / chemistry*


  • Antibodies, Monoclonal
  • Chelating Agents
  • Cobalt Radioisotopes
  • Cross-Linking Reagents
  • Heterocyclic Compounds
  • Imidoesters
  • 6-(4-bromoacetamidobenzyl)-1,4,8,11-tetraazacyclotetradecane-N,N',N'',N'''-tetraacetic acid
  • 4-bromoacetamidobenzyl-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid
  • methyl 4-mercaptobutyrimidate