Synthesis and Biological Characterization of Monomeric and Tetrameric RGD‐Cryptophycin Conjugates

Adina Borbély, Fabién Thoreau, Eduard Figueras, Malika Kadri, Jean-Luc Coll, Didier Boturyn, Norbert Sewald
2020 Chemistry - A European Journal  
The effective delivery of cytotoxic agents to 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. Herein, we report the synthesis and biological evaluation of a multimeric conjugate containing the high-affinity integrin αv β3 binding ligand RAFT-c(RGDfK)4 , a lysosomally cleavable Val-Cit linker, and
more » ... 5 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 αv β3 overexpressing tumor cell lines, while significantly reduced activity was observed in the integrin-negative cell line.
doi:10.1002/chem.201905437 pmid:31943410 pmcid:PMC7064988 fatcat:zjowirffvzh7lh5gpcwepkwxgm