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Review

Exploring Serum Transferrin Regulation of Nonferric Metal Therapeutic Function and Toxicity

1
Department of Chemistry, University of Puerto Rico, Río Piedras Campus, Río Piedras, PR 00931, USA
2
Departamento de Química y Bioquímica, Facultad de Ciencias e Ingeniería, Universidad de Boyacá, Tunja 150003, Colombia
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Inorganics 2020, 8(9), 48; https://doi.org/10.3390/inorganics8090048
Received: 8 August 2020 / Revised: 19 August 2020 / Accepted: 24 August 2020 / Published: 29 August 2020
(This article belongs to the Special Issue Metal Complexes with Biological Functions)
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. View Full-Text
Keywords: serum transferrin; endocytosis; nonferric metal ions; metal transport; bioavailability; bioactivity; metal therapeutic function and toxicity serum transferrin; endocytosis; nonferric metal ions; metal transport; bioavailability; bioactivity; metal therapeutic function and toxicity
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MDPI and ACS Style

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. https://doi.org/10.3390/inorganics8090048

AMA Style

Benjamín-Rivera JA, Cardona-Rivera AE, Vázquez-Maldonado ÁL, Dones-Lassalle CY, Pabón-Colon HL, Rodríguez-Rivera HM, Rodríguez I, González-Espiet JC, Pazol J, Pérez-Ríos JD, Catala-Torres JF, Carrasquillo Rivera M, De Jesus-Soto MG, Cordero-Virella NA, Cruz-Maldonado PM, González-Pagan P, Hernández-Ríos R, Gaur K, Loza-Rosas SA, Tinoco AD. Exploring Serum Transferrin Regulation of Nonferric Metal Therapeutic Function and Toxicity. Inorganics. 2020; 8(9):48. https://doi.org/10.3390/inorganics8090048

Chicago/Turabian Style

Benjamín-Rivera, Josué A., Andrés E. Cardona-Rivera, Ángel L. Vázquez-Maldonado, Christian Y. Dones-Lassalle, Héctor L. Pabón-Colon, Héctor M. Rodríguez-Rivera, Israel Rodríguez, Jean C. González-Espiet, Jessika Pazol, Jobaniel D. Pérez-Ríos, José F. Catala-Torres, Marielie Carrasquillo Rivera, Michael G. De Jesus-Soto, Nicolle A. Cordero-Virella, Paola M. Cruz-Maldonado, Patricia González-Pagan, Raul Hernández-Ríos, Kavita Gaur, Sergio A. Loza-Rosas, and Arthur D. Tinoco 2020. "Exploring Serum Transferrin Regulation of Nonferric Metal Therapeutic Function and Toxicity" Inorganics 8, no. 9: 48. https://doi.org/10.3390/inorganics8090048

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