Improved synthesis and biological evaluation of chelator-modified α-MSH analogs prepared by copper-free click chemistry

Bioorg Med Chem Lett. 2011 Oct 1;21(19):5757-61. doi: 10.1016/j.bmcl.2011.08.017. Epub 2011 Aug 8.

Abstract

Radionuclide chelators (DOTA, NOTA) functionalized with a monofluorocyclooctyne group were prepared. These materials reacted rapidly and in high yield with a fully deprotected azide-modified peptide via Cu-free click chemistry under mild reaction conditions (aqueous solution, room temperature). The resulting bioconjugates bind with high affinity and specificity to their cell-surface receptor targets in vitro and appear stable to degradation in mouse serum over 3h of incubation at 37°C.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Azides
  • Cell Line, Tumor
  • Chelating Agents / chemical synthesis
  • Chelating Agents / chemistry*
  • Click Chemistry / methods*
  • Copper
  • Copper Radioisotopes / chemistry
  • Drug Evaluation, Preclinical
  • Drug Stability
  • Gallium Radioisotopes / chemistry
  • Heterocyclic Compounds / chemistry
  • Heterocyclic Compounds, 1-Ring / chemistry
  • Humans
  • Mice
  • Protein Binding
  • Radiopharmaceuticals / chemical synthesis*
  • Radiopharmaceuticals / chemistry
  • Radiopharmaceuticals / metabolism
  • Sensitivity and Specificity
  • alpha-MSH / analogs & derivatives*
  • alpha-MSH / chemistry*
  • alpha-MSH / metabolism

Substances

  • Azides
  • Chelating Agents
  • Copper Radioisotopes
  • Gallium Radioisotopes
  • Heterocyclic Compounds
  • Heterocyclic Compounds, 1-Ring
  • Radiopharmaceuticals
  • 1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid
  • 1,4,7-triazacyclononane-N,N',N''-triacetic acid
  • alpha-MSH
  • Copper