Exploring Serum Transferrin Regulation of Nonferric Metal Therapeutic Function and Toxicity
Category
Published on
Type
journal-article
Author
Josué A. Benjamín-Rivera and Andrés E. Cardona-Rivera and Ángel L. Vázquez-Maldonado and Christian Y. Dones-Lassalle and Héctor L. Pabón-Colon and Héctor M. Rodríguez-Rivera and Israel Rodríguez and Jean C. González-Espiet and Jessika Pazol and Jobaniel D. Pérez-Ríos and José F. Catala-Torres and Marielie Carrasquillo Rivera and Michael G. De Jesus-Soto and Nicolle A. Cordero-Virella and Paola M. Cruz-Maldonado and Patricia González-Pagan and Raul Hernández-Ríos and Kavita Gaur and Sergio A. Loza-Rosas and Arthur D. Tinoco
Citation
Benjamín-Rivera, J.A. et al., 2020. Exploring Serum Transferrin Regulation of Nonferric Metal Therapeutic Function and Toxicity. Inorganics, 8(9), p.48. Available at: http://dx.doi.org/10.3390/inorganics8090048.
Abstract
Serum transferrin (sTf) plays a pivotal role in regulating iron biodistribution and homeostasis within the body. The molecular details of sTf Fe(III) binding blood transport, and cellular delivery through transferrin receptor-mediated endocytosis are generally well-understood. Emerging interest exists in exploring sTf complexation of nonferric metals as it facilitates the therapeutic potential and toxicity of several of them. This review explores recent X-ray structural and physiologically relevant metal speciation studies to understand how sTf partakes in the bioactivity of key non-redox active hard Lewis acidic metals. It challenges preconceived notions of sTf structure function correlations that were based exclusively on the Fe(III) model by revealing distinct coordination modalities that nonferric metal ions can adopt and different modes of binding to metal-free and Fe(III)-bound sTf that can directly influence how they enter into cells and, ultimately, how they may impact human health. This knowledge informs on biomedical strategies to engineer sTf as a delivery vehicle for metal-based diagnostic and therapeutic agents in the cancer field. It is the intention of this work to open new avenues for characterizing the functionality and medical utility of nonferric-bound sTf and to expand the significance of this protein in the context of bioinorganic chemistry.
DOI
Funding
NSF-STC Biology with X-ray Lasers (NSF-1231306)
