Synthesis and Biological Characterization of Monomeric and Tetrameric RGD-Cryptophycin Conjugates
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 α v β 3 binding 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 α v β 3 overexpressing tumor cell lines, while significantly reduced activity was observed in the integrin-negative cell line.
Références
- Titre
- Synthesis and Biological Characterization of Monomeric and Tetrameric RGD-Cryptophycin Conjugates
- Type de publication
- Article de revue
- Année de publication
- 2020
- Auteurs
- Borbély, Adina, Thoreau Fabien, Figueras Eduard, Kadri Malika, Coll Jean-Luc, Boturyn Didier, and Sewald Norbert
- Revue
- Chemistry – A European Journal
- Volume
- 26
- Pagination
- 2602 – 2605
- Date de publication
- 01/2020
- Type of Article
- Communication
Soumis le 15 janvier 2020