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

Borbely, A; Thoreau, F; Figueras, E; Kadri, M; Coll, J-L; Boturyn, D; Sewald, N; (2020) Synthesis and Biological Characterization of Monomeric and Tetrameric RGD-Cryptophycin Conjugates. Chemistry - A European Journal 10.1002/chem.201905437. Green open access

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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 αvβ3 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 αvβ3 overexpressing tumor cell lines, while significantly reduced activity was observed in the integrin‐negative cell line.

Type: Article
Title: Synthesis and Biological Characterization of Monomeric and Tetrameric RGD-Cryptophycin Conjugates
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/chem.201905437
Publisher version: https://doi.org/10.1002/chem.201905437
Language: English
Additional information: This is an open access article under the terms of Creative Commons Attribution NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
Keywords: Science & Technology, Physical Sciences, Chemistry, Multidisciplinary, Chemistry, antitumor agents, drug delivery, integrins, multivalency, small-molecule drug conjugates, INTEGRIN, ALPHA(V)BETA(3), THERAPY, EXPRESSION, STRATEGIES, MOUSE
UCL classification: UCL
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > Dept of Chemistry
URI: https://discovery.ucl.ac.uk/id/eprint/10092109
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