Deferasirox-TAT(47–57) peptide conjugate as a water soluble, bifunctional iron chelator with potential use in neuromedicine

Deferasirox (DFX), an orally active and clinically approved iron chelator, is being used extensively for the treatment of iron overload. However, its water insolubility makes it cumbersome for practical use. In addition to this, the low efficacy of DFX to remove brain iron prompted us to synthesize...

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Bibliographic Details
Published in:Biometals 2015-10, Vol.28 (5), p.869-877
Main Authors: Goswami, Dibakar, Vitorino, Hector A., Alta, Roxana Y. P., Silvestre, Daniel M., Nomura, Cassiana S., Machini, M. Teresa, Espósito, Breno P.
Format: Article
Language:eng ; dut
Subjects:
Animals
Benzoates - administration & dosage
Benzoates - chemical synthesis
Benzoates - chemistry
Biochemistry
Biomedical and Life Sciences
Biosynthesis
Biotechnology
Blood-brain barrier
Blood-Brain Barrier - drug effects
Cell Biology
Cell Line
Cell Membrane - chemistry
Cell Membrane - drug effects
Chelating
Chelation
Conjugates
Humans
Iron
Iron Chelating Agents - administration & dosage
Iron Chelating Agents - chemical synthesis
Iron Chelating Agents - chemistry
Iron Overload - drug therapy
Iron Overload - pathology
Life Sciences
Medicine/Public Health
Microbiology
Neurological disorders
Peptide Fragments - administration & dosage
Peptide Fragments - chemical synthesis
Peptide Fragments - chemistry
Peptides
Permeability
Pharmacology/Toxicology
Plant Physiology
Rats
Solubility
tat Gene Products, Human Immunodeficiency Virus - administration & dosage
tat Gene Products, Human Immunodeficiency Virus - chemical synthesis
tat Gene Products, Human Immunodeficiency Virus - chemistry
Triazoles - administration & dosage
Triazoles - chemical synthesis
Triazoles - chemistry
Water - chemistry
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Summary:Deferasirox (DFX), an orally active and clinically approved iron chelator, is being used extensively for the treatment of iron overload. However, its water insolubility makes it cumbersome for practical use. In addition to this, the low efficacy of DFX to remove brain iron prompted us to synthesize and evaluate a DFX-TAT(47–57) peptide conjugate for its iron chelation properties and permeability across RBE4 cell line, an in vitro model of the blood–brain barrier. The water-soluble conjugate was able to remove labile iron from buffered solution as well as from iron overloaded sera, and the permeability of DFX-TAT(47–57) conjugate into RBE4 cells was not affected compared to parent deferasirox. The iron bound conjugate was also able to translocate through the cell membrane.
ISSN:0966-0844
1572-8773
DOI:10.1007/s10534-015-9873-5