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

被引:248
作者
Thumshirn, G
Hersel, U
Goodman, SL
Kessler, H
机构
[1] Tech Univ Munich, Inst Organ Chem & Biochem, D-85747 Garching, Germany
[2] Merck KGaA, Oncol Res, D-64271 Darmstadt, Germany
关键词
chemoselective ligation; integrin; multimer; peptides; tumor targeting;
D O I
10.1002/chem.200204304
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
The alphavbeta3 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-trimethylstannyl-benzaldehyde results in a precursor for radioiododestannylation, which would allow them to be used as potential tools for targeting and imaging alphavbeta3-expressing tumor cells. The conjugates were obtained in good yield without the need of a protection strategy and under mild conditions.
引用
收藏
页码:2717 / 2725
页数:9
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