NEWS

New paper published in Nature Chemical Biology!

“Minimizing higher-order aggregation maximizes iron mobilization by small molecules”

The natural product hinokitiol mobilizes iron across lipid bilayers at low concentrations and restores hemoglobinization in iron transporter protein-deficient systems. But hinokitiol fails to similarly mobilize iron at higher concentrations, limiting its uses in chemical biology and medicine. Here we show that at higher concentrations, hinokitiol₃:Fe(III) complexes form large, higher-order aggregates, leading to loss of transmembrane iron mobilization. Guided by this understanding and systematic structure–function studies enabled by modular synthesis, we identified FeM-1269, which minimally aggregates and dose-dependently mobilizes iron across lipid bilayers even at very high concentrations. In contrast to hinokitiol, FeM-1269 is also well-tolerated in animals at high doses for extended periods of time. In a mouse model of anemia of inflammation, FeM-1269 increases serum iron, transferrin saturation, hemoglobin and hematocrit. This rationally developed iron-mobilizing small molecule has enhanced potential as a molecular prosthetic for understanding and potentially treating iron transporter deficiencies.

Read the paper here: https://www.nature.com/articles/s41589-024-01596-3

Welcome, Bingcong and Delores!

We warmly welcome Bingcong and Delores, MS students in the Nutritional Sciences program, to the Seo lab!

Welcome, Sangnam and Yuka!

We warmly welcome Sangnam and Yuka to the Seo lab!

2019 Iwase & Seo lab Christmas Party!