Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Exploring Serum Transferrin Regulation of Nonferric Metal Therapeutic Function and Toxicity

Version 1 : Received: 8 August 2020 / Approved: 9 August 2020 / Online: 9 August 2020 (21:47:51 CEST)

A peer-reviewed article of this Preprint also exists.

Benjamín-Rivera, J.A.; Cardona-Rivera, A.E.; Vázquez-Maldonado, Á.L.; Dones-Lassalle, C.Y.; Pabón-Colon, H.L.; Rodríguez-Rivera, H.M.; Rodríguez, I.; González-Espiet, J.C.; Pazol, J.; Pérez-Ríos, J.D.; Catala-Torres, J.F.; Carrasquillo Rivera, M.; De Jesus-Soto, M.G.; Cordero-Virella, N.A.; Cruz-Maldonado, P.M.; González-Pagan, P.; Hernández-Ríos, R.; Gaur, K.; Loza-Rosas, S.A.; Tinoco, A.D. Exploring Serum Transferrin Regulation of Nonferric Metal Therapeutic Function and Toxicity. Inorganics 2020, 8, 48. Benjamín-Rivera, J.A.; Cardona-Rivera, A.E.; Vázquez-Maldonado, Á.L.; Dones-Lassalle, C.Y.; Pabón-Colon, H.L.; Rodríguez-Rivera, H.M.; Rodríguez, I.; González-Espiet, J.C.; Pazol, J.; Pérez-Ríos, J.D.; Catala-Torres, J.F.; Carrasquillo Rivera, M.; De Jesus-Soto, M.G.; Cordero-Virella, N.A.; Cruz-Maldonado, P.M.; González-Pagan, P.; Hernández-Ríos, R.; Gaur, K.; Loza-Rosas, S.A.; Tinoco, A.D. Exploring Serum Transferrin Regulation of Nonferric Metal Therapeutic Function and Toxicity. Inorganics 2020, 8, 48.

Journal reference: Inorganics 2020, 8, 48
DOI: 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.

Subject Areas

Serum transferrin; endocytosis; nonferric metal ions; metal transport, bioavailability, and bioactivity; metal therapeutic function and toxicity

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