Multimeric Cyclic RGD Peptides as Potential Tools for Tumor Targeting: Solid‐Phase Peptide Synthesis and Chemoselective Oxime Ligation

Abstract

The αvβ3 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 αvβ3-expressing tumor cells. The conjugates were obtained in good yield without the need of a protection strategy and under mild conditions.