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Chelator-peptide conjugates permeable to the blood-brain barrier as protectors against iron-induced toxicity

Grant number: 11/18958-0
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): November 01, 2012
Effective date (End): October 31, 2014
Field of knowledge:Physical Sciences and Mathematics - Chemistry - Inorganic Chemistry
Principal researcher:Breno Pannia Esposito
Grantee:Dibakar Goswami
Home Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:11/50318-1 - Development of compounds with pharmacological or medicinal interest and of systems for their transport, detection and recognition in biological media, AP.TEM


The blood-brain barrier (BBB)-shielding function provided by endothelial cells is important in the treatment of neurological diseases, because this exclusion of foreign substances also restricts the entry of many potentially therapeutic agents into the brain. Recently, potential applications of iron chelators e.g. Deferiprone, Deferasirox, Desferrioxamine and others for clinical management of neuodegenerative diseases have attracted attention. Since these chelators have limited ability to cross the BBB on their own, several peptides e.g. TAT-peptide and penetratin, which have the potential to cross BBB, can be used as delivery vectors for these chelators. These peptides will be synthesized following solid state peptide synthesis techniques, and will be conjugated to the iron chelators. Fe-binding ability of the conjugates, their ability to decrease plasmatic or cytossolic pools of labile iron, and also the comparative effects of externally added pro-oxidants (such as H2O2) on Fe-catalysed generation of reactive species upon binding with the new chelators will be assessed.

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
GOSWAMI, DIBAKAR; VITORINO, HECTOR A.; ALTA, ROXANA Y. P.; SILVESTRE, DANIEL M.; NOMURA, CASSIANA S.; TERESA MACHINI, M.; ESPOSITO, BRENO P.. Deferasirox-TAT(47-57) peptide conjugate as a water soluble, bifunctional iron chelator with potential use in neuromedicine. BIOMETALS, v. 28, n. 5, p. 869-877, . (11/18958-0)
GOSWAMI, DIBAKAR; VITORINO, HECTOR AGUILAR; TERESA MACHINI, M.; ESPOSITO, BRENO P.. Self-assembled penetratin-deferasirox micelles as potential carriers for hydrophobic drug delivery. Biopolymers, v. 104, n. 6, p. 712-719, . (11/18958-0)

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