Multimeric cyclic RGD peptides as potential tools for tumor targeting: solid-phase peptide synthesis and chemoselective oxime ligation

Chemistry. 2003 Jun 16;9(12):2717-25. doi: 10.1002/chem.200204304.

Abstract

The alpha v beta 3 integrin receptor plays an important role in human metastasis and tumor-induced angiogenesis. Targeting this receptor may provide information about the receptor status of the tumor and enable specific therapeutic planning. Solid-phase peptide synthesis of multimeric cyclo(-RGDfE-)-peptides is described, which offer the possibility of enhanced integrin targeting due to polyvalency effects. These peptides contain an aminooxy group for versatile chemoselective oxime ligation. Conjugation with para-trimethylstannylbenzaldehyde results in a precursor for radioiododestannylation, which would allow them to be used as potential tools for targeting and imaging alpha v beta 3-expressing tumor cells. The conjugates were obtained in good yield without the need of a protection strategy and under mild conditions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Integrin alphaVbeta3 / antagonists & inhibitors
  • Integrin alphaVbeta3 / metabolism
  • Mice
  • Mice, Nude
  • Neoplasms, Experimental / metabolism
  • Oligopeptides / chemical synthesis*
  • Oligopeptides / pharmacology
  • Oximes / chemical synthesis*
  • Oximes / pharmacology
  • Peptides, Cyclic / chemical synthesis*
  • Peptides, Cyclic / pharmacology
  • Vitronectin / antagonists & inhibitors
  • Vitronectin / metabolism

Substances

  • Integrin alphaVbeta3
  • Oligopeptides
  • Oximes
  • Peptides, Cyclic
  • Vitronectin
  • arginyl-glycyl-aspartic acid