Journal
BIOMETALS
Volume 28, Issue 5, Pages 869-877Publisher
SPRINGER
DOI: 10.1007/s10534-015-9873-5
Keywords
Deferasirox; Iron; Tat; Peptide; Blood-brain barrier; Overload; Chelation
Categories
Funding
- Sao Paulo Research Foundation (FAPESP) [11/18958-0]
- FAPESP
- CNPq
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [11/18958-0] Funding Source: FAPESP
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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.
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