Synthesis and Properties of a Mitochondrial Peripheral Benzodiazepine Receptor Conjugate

Abdessamad El Alaoui; Frédéric Schmidt; Marianne Sarr; Didier Decaudin; Jean‐Claude Florent; Ludger Johannes

doi:10.1002/cmdc.200800249

journal article Nov 06, 2008

Synthesis and Properties of a Mitochondrial Peripheral Benzodiazepine Receptor Conjugate

Abdessamad El Alaoui Frédéric Schmidt

Marianne Sarr Didier Decaudin Jean‐Claude Florent Ludger Johannes

ChemMedChem Vol. 3 No. 11 pp. 1687-1695 · Wiley

View at Publisher Save 10.1002/cmdc.200800249

Abstract

AbstractPeripheral benzodiazepine receptors are potential targets for cancer therapeutics through the use of specific ligands such as the pro‐apoptotic benzodiazepine RO5‐4864. However, the poor water solubility of this compound has been a limitation to its application in vivo. Herein we describe an efficient synthesis for the conjugation, via a cleavable linker arm, of RO5‐4864 to a novel tumour‐delivery tool, the B‐subunit of Shiga toxin (STxB). The conjugate is water soluble and specifically targets cancer cells that overexpress the glycolipid Gb3, the cellular Shiga toxin receptor that is found on several human tumours. After internalisation via retrograde transport, the prodrug is cleaved inside cells to release the active principle. Delivery by STxB therefore increases the cytotoxic activity of RO5‐4864 and its tumour specificity.

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References

Details

Published: Nov 06, 2008
Vol/Issue: 3(11)
Pages: 1687-1695
License: View

Authors

1Centre de Recherche, Institut Curie, CNRS UMR144, Paris, France;

D

Didier Decaudin

From the Laboratoire d'Imagerie Moléculaire Expérimentale, Commissariat à l'Energie Atomique, Institut d'Imagerie Biomédicale, Orsay, France; Laboratoire de Trafic, Signalisation et Ciblage Intracellulaires, Laboratoire d'Hématologie Clinique, Laboratoire d'Investigation Préclinique, Département de Transfert, Institut Curie, Paris, France; Centre National de la Recherche Scientifique Unité Mixte de Recherche 144, Paris, France; and Laboratoire de recherche sur la réparation et la transcription dans les...

Cite This Article

Abdessamad El Alaoui, Frédéric Schmidt, Marianne Sarr, et al. (2008). Synthesis and Properties of a Mitochondrial Peripheral Benzodiazepine Receptor Conjugate. ChemMedChem, 3(11), 1687-1695. https://doi.org/10.1002/cmdc.200800249

Synthesis and Properties of a Mitochondrial Peripheral Benzodiazepine Receptor Conjugate

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