Propylene cross-bridged macrocyclic bifunctional chelator: a new design for facile bioconjugation and robust (64)Cu complex stability

J Med Chem. 2014 Sep 11;57(17):7234-43. doi: 10.1021/jm500348z. Epub 2014 Aug 26.

Abstract

The first macrocyclic bifunctional chelator incorporating propylene cross-bridge was efficiently synthesized from cyclam in seven steps. After the introduction of an extra functional group for facile conjugation onto the propylene cross-bridge, the two carboxylic acid pendants could contribute to strong coordination of Cu(II) ions, leading to a robust Cu complex. The cyclic RGD peptide conjugate of PCB-TE2A-NCS was prepared and successfully radiolabeled with (64)Cu ion. The radiolabeled peptide conjugate was evaluated in vivo through a biodistribution study and animal PET imaging to demonstrate high tumor uptake with low background.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkenes / chemistry*
  • Animals
  • Chelating Agents / chemical synthesis
  • Chelating Agents / chemistry*
  • Chelating Agents / pharmacokinetics
  • Coordination Complexes / chemistry
  • Copper / chemistry*
  • Copper Radioisotopes / chemistry
  • Copper Radioisotopes / pharmacokinetics
  • Drug Design*
  • Glioblastoma / metabolism
  • Glioblastoma / pathology
  • Heterocyclic Compounds / chemistry
  • Humans
  • Macrocyclic Compounds / chemical synthesis
  • Macrocyclic Compounds / chemistry*
  • Mice
  • Mice, Nude
  • Models, Chemical
  • Molecular Structure
  • Oligopeptides / chemistry
  • Positron-Emission Tomography / methods
  • Rats
  • Tissue Distribution
  • Transplantation, Heterologous

Substances

  • Alkenes
  • Chelating Agents
  • Coordination Complexes
  • Copper Radioisotopes
  • Heterocyclic Compounds
  • Macrocyclic Compounds
  • Oligopeptides
  • cyclam
  • Copper
  • arginyl-glycyl-aspartic acid
  • propylene