A robust and convergent synthesis of dipeptide-DOTAM conjugates as chelators for lanthanide ions: new PARACEST MRI agents

Bioconjug Chem. 2007 Sep-Oct;18(5):1625-36. doi: 10.1021/bc0701287. Epub 2007 Aug 22.

Abstract

A generally applicable synthetic approach to dipeptide-DOTAM conjugates has been developed which is based on the peralkylation of 1,4,7,10-tetraazacyclododecane (cyclen) with protected N-iodoacetyl dipeptides. Standardized procedures were used for the alkylation, metalation, and purification of the resultant lanthanide complexes. Using this approach, we have been able to rapidly and reliably prepare and screen five different ligands each with up to six lanthanide ions. This preliminary investigation has identified several paramagnetic compounds with strong chemical exchange saturation transfer (PARACEST) properties in water at physiological temperature and pH. Extension of the synthetic approach to a wide variety of amino acids is possible.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetamides / chemical synthesis*
  • Alkylation
  • Chelating Agents / chemical synthesis*
  • Contrast Media / chemistry*
  • Cyclams
  • Dipeptides / chemical synthesis*
  • Heterocyclic Compounds / chemistry
  • Heterocyclic Compounds, 1-Ring / chemical synthesis*
  • Hydrogen-Ion Concentration
  • Ions
  • Lanthanoid Series Elements / chemistry*
  • Ligands
  • Magnetic Resonance Imaging
  • Models, Chemical
  • Organometallic Compounds / chemical synthesis*
  • Temperature

Substances

  • 1,4,7,10-tetrakis(carbamoylmethyl)-1,4,7,10-tetraazacyclododecane
  • Acetamides
  • Chelating Agents
  • Contrast Media
  • Cyclams
  • Dipeptides
  • Heterocyclic Compounds
  • Heterocyclic Compounds, 1-Ring
  • Ions
  • Lanthanoid Series Elements
  • Ligands
  • Organometallic Compounds
  • cyclen