Synthesis and Biological Characterization of Monomeric and Tetrameric RGD‐Cryptophycin Conjugates
Résumé
The effective delivery of cytotoxic agents to the tumor cells is a key challenge in anticancer therapy. Multivalent integrinspecific ligands are considered a promising tool to increase the binding affinity, selectivity, and internalization efficiency of small molecule-drug conjugates. Here we report the synthesis and biological evaluation of a multimeric conjugate containing the high-affinity integrin αvβ3binding ligand RAFT-c(RGDfK)4, a lysosomally cleavable Val-Cit linker and cryptophycin-55 glycinate, a potent inhibitor of tubulin polymerization. In vitro cytotoxicity assays verified that the multimeric RGD-cryptophycin conjugate displays improved potency compared to the monomeric analogue in integrin αvβ3overexpressing tumor cell lines, while significantly reduced activity was observed in the antigen-negative cell line
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