A stable meta-carborane enables the generation of boron-rich peptide agonists targeting the ghrelin receptor

Journal of Peptide Science : an Official Publication of the European Peptide Society
Dennis J WormAnnette G Beck-Sickinger

Abstract

Boron neutron capture therapy (BNCT) is a binary cancer therapy, which combines the biochemical targeting of a boron-containing drug with the regional localization of radiation treatment. Although the concept of BNCT has been known for decades, the selective delivery of boron into tumor cells remains challenging. G protein-coupled receptors that are overexpressed on cancer cells in combination with peptidic ligands can be potentially used as shuttle system for a tumor-directed boron uptake. In this study, we present the generation of short, boron-rich peptide conjugates that target the ghrelin receptor. Expression of the ghrelin receptor on various cancer cells makes it a viable target for BNCT. We designed a novel hexapeptide super-agonist that was modified with different specifically synthesized carborane monoclusters and tested for ghrelin receptor activation. A meta-carborane building block with a mercaptoacetic acid linker was found to be optimal for peptide modification, owing to its chemical stability and a suitable activation efficacy of the conjugate. The versatility of this carborane for the development of peptidic boron delivery agents was further demonstrated by the generation of highly potent, boron-loaded conjugat...Continue Reading

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Citations

Nov 25, 2018·ChemMedChem·Evamarie Hey-HawkinsDanijelа Maksimovic-Ivanic
Jun 25, 2019·Angewandte Chemie·Zhongming YangHong Yan
Dec 7, 2019·Dalton Transactions : an International Journal of Inorganic Chemistry·Martin KellertEvamarie Hey-Hawkins
Aug 1, 2020·Frontiers in Chemistry·Paul HoppenzAnnette G Beck-Sickinger
Sep 13, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Martin KellertEvamarie Hey-Hawkins
Dec 30, 2020·Angewandte Chemie·Meng ChenHong Yan
May 1, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Martin KellertEvamarie Hey-Hawkins
May 4, 2021·Journal of Peptide Science : an Official Publication of the European Peptide Society·Philipp Wolf, Annette G Beck-Sickinger

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