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Synthesis and Biological Characterization of Monomeric and Tetrameric RGD-Cryptophycin Conjugates.

ABSTRACT: 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 α_v β₃ 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 β₃ overexpressing tumor cell lines, while significantly reduced activity was observed in the integrin-negative cell line.

SUBMITTER: Borbely A

PROVIDER: S-EPMC7064988 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Synthesis and Biological Characterization of Monomeric and Tetrameric RGD-Cryptophycin Conjugates.

Borbély Adina A Thoreau Fabien F Figueras Eduard E Kadri Malika M Coll Jean-Luc JL Boturyn Didier D Sewald Norbert N

Chemistry (Weinheim an der Bergstrasse, Germany) 20200211 12

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 V ...[more]

PMID: 31943410

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