Title:

Synthesis of a Hexadentate Chelator Linker for Attachment to a Mitochondria Seeking Peptide

Iron is an essential nutrient that facilitates cell growth and proliferation. In the mitochondrion, iron enables enzymes involved in respiratory complexes, DNA synthesis, the cell cycle, detoxifying enzymes, and more.1 Cancer cells have been shown to upregulate iron intake.1 Current approaches have focused on interfering with the ability of cancer cells to use iron by directly modulating iron-regulated genes or by the use of iron chelators, however selectivity of cancer cells remains a challenge.1 This research aims to synthesize a hexadentate iron chelator linker attached to a mitochondria seeking peptide for study of the mitochondrial labile iron pool. Some cancers have been shown to upregulate respiration, increasing mitochondria concentrations. This coupled with increased labile iron pools in cancer cells may cause our probe to show increased selectivity.2 The target molecule is an 8-hydroxyquinoline based tripodal structure linked to a mitochondrial seeking tetrapeptide through amide linkage. 8-hydroxyquinoline alone has been shown to effectively bind iron and the delivery of three equivalents of this molecule to the mitochondria should demonstrate increased iron binding. Currently, progress has been made in the synthesis of the target molecule. References: 1. Jung, M., Mertens, C., Tomat, E., & Brüne, B. (2019). Iron as a Central Player and Promising Target in Cancer Progression. International journal of molecular sciences, 20(2), 273. https://doi.org/10.3390/ijms20020273 2. Wallace D. C. (2012). Mitochondria and cancer. Nature reviews. Cancer, 12(10), 685–698. https://doi.org/10.1038/nrc3365

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