Identification of a novel BODIPY minihepcidin tool for the high content analysis of ferroportin (SLC40A1) pharmacology

Abstract

Iron is essential to life and is actively absorbed by enterocytes and secreted into plasma by the iron exporter ferroportin (SLC40A1). Dysregulation of iron homeostasis is a key component of many diseases such as hemochromatosis and beta-thalassemia. Ferroportin is the only known iron exporter protein, and as such is an important therapeutic target. To-date, modulators of ferroportin activity have shown promise in pre-clinical models, with recent screening assays enabling screening in a high throughput “loss of signal” format. Herein, we describe the design and synthesis of a novel BODIPY-labelled minihepcidin peptide to enable the high content analysis of ferroportin (SLC40A1) pharmacology, and the high throughput screening of compounds in a “gain of signal” assay format.